Improving the forecast for biodiversity under climate change.

New biological models are incorporating the realistic processes underlying biological responses to climate change and other human-caused disturbances. However, these more realistic models require detailed information, which is lacking for most species on Earth. Current monitoring efforts mainly document changes in biodiversity, rather than collecting the mechanistic data needed to predict future changes. We describe and prioritize the biological information needed to inform more realistic projections of species' responses to climate change. We also highlight how trait-based approaches and adaptive modeling can leverage sparse data to make broader predictions. We outline a global effort to collect the data necessary to better understand, anticipate, and reduce the damaging effects of climate change on biodiversity.

Protease-modulating polyacrylate-based hydrogel stimulates wound bed preparation in venous leg ulcers--a randomized controlled trial.

BACKGROUND: Stringent control of proteolytic activity represents a major therapeutic approach for wound-bed preparation. OBJECTIVES: We tested whether a protease-modulating polyacrylate- (PA-) containing hydrogel resulted in a more efficient wound-bed preparation of venous leg ulcers when compared to an amorphous hydrogel without known protease-modulating properties. METHODS: Patients were randomized to the polyacrylate-based hydrogel (n = 34) or to an amorphous hydrogel (n = 41). Wound beds were evaluated by three blinded experts using photographs taken on days 0, 7 and 14. RESULTS: After 14 days of treatment there was an absolute decrease in fibrin and necrotic tissue of 37.6 ± 29.9 percentage points in the PA-based hydrogel group and by 16.8 ± 23.0 percentage points in the amorphous hydrogel group. The absolute increase in the proportion of ulcer area covered by granulation tissue was 36.0 ± 27.4 percentage points in the PA-based hydrogel group and 14.5 ± 22.0 percentage points in the control group. The differences between the groups were significant (decrease in fibrin and necrotic tissue P = 0.004 and increase in granulation tissue P = 0.0005, respectively). CONCLUSION: In particular, long-standing wounds profited from the treatment with the PA-based hydrogel. These data suggest that PA-based hydrogel dressings can stimulate normalization of the wound environment, particularly in hard-to-heal ulcers.

Foray search: an effective systematic dispersal strategy in fragmented landscapes.

In the absence of evidence to the contrary, population models generally assume that the dispersal trajectories of animals are random, but systematic dispersal could be more efficient at detecting new habitat and may therefore constitute a more realistic assumption. Here, we investigate, by means of simulations, the properties of a potentially widespread systematic dispersal strategy termed "foray search." Foray search was more efficient in detecting suitable habitat than was random dispersal in most landscapes and was less subject to energetic constraints. However, it also resulted in considerably shorter net dispersed distances and higher mortality per net dispersed distance than did random dispersal, and it would therefore be likely to lead to lower dispersal rates toward the margins of population networks. Consequently, the use of foray search by dispersers could crucially affect the extinction-colonization balance of metapopulations and the evolution of dispersal rates. We conclude that population models need to take the dispersal trajectories of individuals into account in order to make reliable predictions.

[Visual documentation of the stability of intravenous solutions of omeprazole (Losec) and pantoprazole (Pantoloc)]. / Visuelle Dokumentation der Stabilität der intravenösen Lösungen von Omeprazol (Losec) und Pantoprazol (Pantoloc).

Patients with complications of peptic ulcers, high grade reflux oesophagitis, or Zollinger Ellison syndrome need a sufficient permanent acid suppression. In appropriate indications they receive proton pump inhibitors (PPI) intravenously or via perfusion over a longer period, if an oral application is not possible. PPIs are prodrugs, which should be converted into the active principle in the acidic canaliculus at pH 1 of the parietal cell. Otherwise they would be activated prematurely. Immediate chemical degradation causes discolouration. Aim of the study was to compare pH stabilities of the intravenous formulations of Omeprazole (different solutions for infusion and injection) and Pantoprazole (one solution for injection and infusion). The solutions prepared accordingly to the official instructions, were exposed to four different light conditions. Both manufacturers (AstraZeneca Osterreich GmbH, Byk Osterreich Pharma Ges.m.b.H.) state reference solutions for acceptable discolouration. Those were prepared according to the European Pharmacopeia. Discolouration of solutions were evaluated as criterion for stability of the PPI prodrugs. If change of colour is at least of the extent of the corresponding reference solution, further use is no longer permitted. Optical alterations under different light conditions were compared and documented photographically with standardized illumination. Intensity and spectral composition of light as well as temperature had only minor influence on discolouration as measure of degradation of the prodrugs. Both formulations for injection fulfill the specifications for pH stability within the stated time frames mentioned in the summaries of product characteristics (SPC). Comparing both products, after a short period (1 hour) Omeprazole injectable formulation showed a substantial optical discolouration. After 6 hours these changes were more intense than the reference solution BG5 allows. Pantoprazole showed optical alteration to a notable later time point. After 24 hours discolouration reached the reference colour B6. Injectable formulation of Pantoprazole is about three times more stable than that of Omeprazole. Infusion solution of Omeprazole shows no optical alteration within the stated time frame due to high dilution and pH value. Assuming that 100 ml of the infusion solution contains 40 mg Omeprazole. It takes 5 hours for the volume to be infused at a dose regimen of 8 mg/h. Therefor 5 x 100 ml/24 h are needed.

Charge-reduced nano electrospray ionization combined with differential mobility analysis of peptides, proteins, glycoproteins, noncovalent protein complexes and viruses.

This study explores the potential of a novel electrospray-based method, termed gas-phase electrophoretic mobility molecular analysis (GEMMA), allowing the molecular mass determination of peptides, proteins and noncovalent biocomplexes up to 2 MDa (dimer of immunglobulin M). The macromolecular ions were formed by nano electrospray ionization (ESI) in the 'cone jet' mode. The multiple charged state of the monodisperse droplets/ions generated was reduced by means of bipolar ionized air (generated by an alpha-particle source) to yield exclusively singly charged positive and negative ions as well as neutrals. These ions are separated subsequently at atmospheric pressure using a nano differential mobility analyzer according to their electrophoretic mobility in air. Finally, the ions are detected using a standard condensation particle counter. Data were expressed as electrophoretic mobility diameters by applying the Millikan equation. The measured electrophoretic mobility diameters, or Millikan diameters, of 32 well-defined proteins were plotted against their molecular weights in the range 3.5 to 1920 kDa and exhibited an excellent squared correlation coefficient (r(2) = 0.999). This finding allowed the exact molecular weight determination of large (glyco)proteins and noncovalent biocomplexes by means of this new technique with a mass accuracy of +/-5.6% up to 2 MDa at the femtomole level. From the molecular masses of the weakly bound, large protein complexes thus obtained, the binding stoichiometry of the intact complex and the complex stability as a function of pH, for example, can be derived. Examples of specific protein complexes, such as the avidin or catalase homo-tetramer, are used to illustrate the potential of the technique for characterization of high-mass biospecific complexes. A discussion of current and future applications of charge-reduced nano ESI GEMMA, such as chemical reaction monitoring (reduction process of immunglobulin G) or size determination of an intact virus, a supramolecular complex, and monitoring of partial dissociation of a human rhinoviruses, is provided.

Reaction monitoring of platinum(II) complex--5'-guanosine monophosphate adduct formation by ion exchange liquid chromatography/electrospray ionization mass spectrometry.

Cisplatin and four structurally related platinum(II) complexes were incubated with guanosine 5'-monophosphate (5'-GMP) in water at 37 degrees C. The adduct formation reactions were monitored with cation- and anion-exchange liquid chromatography/electrospray ionization mass spectrometry. In addition to mono- and bis-adducts of guanosine 5'-monophosphate with the platinum(II) complexes, other molecular species, presumably with a binuclear structure (two platinum(II) centres), were detected in the reaction mixtures, which have not been reported previously, indicating an unexpected complexity of adduct formation. Anion-exchange chromatography revealed the presence of isomers of two complexes which presumably result from the restricted rotation at the platinum-- N-7 (5'-GMP) bonds. All reaction products were characterized in both the positive and negative ion modes. Furthermore, preliminary kinetics and half-times of complex formation were investigated for cisplatin and two other platinum(II) complexes, monitoring the relative concentrations of free 5'-GMP and of mono- and bis-GMP adducts as a function of time (250 h) using an internal standard protocol with thymidine 5'-monophosphate.

Characterization of stationary phases for gas chromatography by 29Si NMR spectroscopy. II. Silphenylene-siloxane copolymers.

A series of tetramethyl-p-silphenylene-siloxane copolymers with dimethyl, 1H,1H,2H,2H-perfluorodecylmethyl and diphenyl siloxy groups was prepared. 1H and 29Si nuclear magnetic resonance spectroscopy showed that the chosen reaction conditions provided polymers with diphenyl content up to 85%. The theoretical content of the monomer units correlated well with the measured content. Signal assignments of the copolymers and their corresponding chemical shifts are summarized. Information about alternating, randomized or block sequences was obtained by 29Si nuclear magnetic resonance spectroscopy. Limitations of the method for the determination of microstructure parameters are discussed.

Determination of the metabolites of nitrofuran antibiotics in animal tissue by high-performance liquid chromatography-tandem mass spectrometry.

A LC-MS-MS method is presented to analyse simultaneously the metabolites of four nitrofuran antibacterial agents, furazolidone, furaltadone, nitrofurazone and nitrofurantoin in animal muscle tissue. Sample clean-up and analyte enrichment was performed by solid-phase extraction (SPE) with a polystyrene sorbent following combined hydrolysis of the protein-bound drug metabolites and derivatisation of the homogenised tissue with 2-nitrobenzaldehyde. Limits of detection of 0.5-5 ng g(-1) tissue and limits of determination of 2.5-10 ng g(-1) tissue were achieved using electrospray ionisation in positive mode. Analyte identification and quantification was performed according to EU guidelines, using multiple reaction monitoring (MRM) with one precursor ion and two product ions as identifiers. The use of an internal standard in combination with the simplified sample preparation led to a sensitive and reliable analysis method. The yield of the derivatisation reaction was between 66 and 74% and the recovery of SPE reached 92-105% for all values between 10 and 500 ng g(-1). The developed analytical protocol has been applied to contaminated tissue samples of furazolidone- and furaltadone-treated pigs and allowed unequivocal identification and quantification of the metabolites.

Determination of zearalenone and its metabolites alpha- and beta-zearalenol in beer samples by high-performance liquid chromatography-tandem mass spectrometry.

A fast, robust and sensitive LC-MS-MS method for the determination of zearalenone (ZON) and its metabolites alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL) in beer samples is described. Sample preparation was performed by direct RP-18 solid-phase extraction of undiluted beer samples followed by selective determination of analytes by LC-MS-MS applying an atmospheric pressure chemical ionization (APCI) interface. Using the negative ion mode limits of determination of 0.03-0.06 microg l(-1) beer and limits of quantification of 0.07-0.15 microg l(-1) beer were achieved, which was distinctly more sensitive than in the positive ion mode. Twenty-three beer samples from different countries, produced from different grains and under different brewing conditions, were investigated by this method, but only in one sample could beta-ZOL and ZON be detected. Independently of the type of beer, relative standard deviations between 2.1% and 3.3%, a linear working range of 0.15 microg l(-1) to 500 microg l(-1) beer and recovery rates around 100% could be achieved when zearalanone (ZAN) was used as internal standard.

Determination of zearalenone and its metabolites in urine and tissue samples of cow and pig by LC-MS/MS.

For the sensitive and selective determination of zeranol, taleranol, α-zearalenol, ß-zearalenol and zearalenone in animal urine and tissue a LC-MS/MS method has been developed. Sample preparation included extraction of meat samples and enzymatic digest of urine samples followed by solid-phase extraction with RP-18 columns for sample clean-up. Mass spectrometric determination was carried out with an atmospheric pressure chemical ionisation interface (APCI) in the multi-reaction monitoring mode (MRM). Using the negative ion mode detection limits between 0.1 and 0.5 ppb and determination limits between 0.5 and 1 ppb could be achieved. With zearalanone as internal standard, a linear range between 0.5 (1.0) and 100 ppb in urine samples (cow; pig) and between 1 and 100 ppb in meat samples (cow, calf, pig) could be established. Depending on the biological matrix and analyte standard deviations were below 8.2 %, with recovery rates between 86 and 102 % in spiked samples. The applicability of the method was demonstrated via several contaminated cow and pig urine samples.

Determination of zearalenone in grains by high-performance liquid chromatography-tandem mass spectrometry after solid-phase extraction with RP-18 columns or immunoaffinity columns.

In this paper a robust, sensitive and selective LC-MS-MS method for the determination of zearalenone (ZON) in several cereals is described. Sample preparation was performed by extraction of the commodities with a mixture of acetonitrile and water followed by solid-phase extraction with RP-18 columns or immunoaffinity columns. The selective determination of ZON was achieved with an atmospheric pressure chemical ionization interface. Using the negative ion mode a detection limit of 0.5 microg/kg and a determination limit of 1 microg/kg grain was achieved, which is by a factor of 100 more sensitive than the positive ion mode. Zearalanone (ZAN), which does not occur in nature, was used as internal standard for quantification. A linear working range from 1.0 microg/kg to 1000 microg/kg could be achieved in grains with a standard deviation of 4% and recovery rates around 100%. All these results were independent from the grain matrices (maize, barley, oats, wheat) when ZAN was used as internal standard. Sample preparation with RP-18 and immunoaffinity materials gave comparable results. In addition, the method was successfully used for the investigation of naturally contaminated maize samples in the course of an interlaboratory comparison test.

Cell wall structural divergence among Thermus spp.

The fine structure of sacculi from Thermus thermophilus HB27, T. aquaticus YT-1 and Thermus ATCC27737 has been worked out by HPLC analysis and mass spectrometry techniques. The three microorganisms have a murein composition of the rare A3beta chemotype, but showed substantial differences in muropeptide composition. Phenylacetylated muropeptides,previously described in T. thermophilus HB8, were detected exclusively in T. thermophilus HB27. Murein from T. aquaticusYT-1 was devoid of D-Ala-D-Ala terminated muropeptides, which were, in contrast, abundant in T. thermophilus HB27 and Thermus ATCC27737. The significance of these findings is discussed.

Peptidoglycan structural dynamics during germination of Bacillus subtilis 168 endospores.

Peptidoglycan structural dynamics during endospore germination of Bacillus subtilis 168 have been examined by muropeptide analysis. The first germination-associated peptidoglycan structural changes are detected within 3 min after the addition of the specific germinant L-alanine. We detected in the spore-associated material new muropeptides which, although they have slightly longer retention times by reversed-phase (RP)-high-pressure liquid chromatography (HPLC) than related ones in dormant spores, show the same amino acid composition and molecular mass. Two-dimensional nuclear magnetic resonance (NMR) analysis shows that the chemical changes to the muropeptides on germination are minor and are probably limited to stereochemical inversion. These new muropeptides account for almost 26% of the total muropeptides in spore-associated material after 2 h of germination. The exudate of germinated spores of B. subtilis 168 contains novel muropeptides in addition to those present in spore-associated material. Exudate-specific muropeptides have longer retention times, have no reducing termini, and exhibit a molecular mass 20 Da lower than those of related reduced muropeptides. These new products are anhydro-muropeptides which are generated by a lytic transglycosylase, the first to be identified in a gram-positive bacterium. There is also evidence for the activity of a glucosaminidase during the germination process. Quantification of muropeptides in spore-associated material indicates that there is a heterogeneous distribution of muropeptides in spore peptidoglycan. The spore-specific residue, muramic delta-lactam, is proposed to be a major substrate specificity determinant of germination-specific lytic enzymes, allowing cortex hydrolysis without any effect on the primordial cell wall.

Peptidoglycan structure of Salmonella typhimurium growing within cultured mammalian cells.

The cell wall structure of Salmonella typhimurium has been studied for the first time during transit from free-living to parasitic lifestyles. Peptidoglycan of S. typhimurium proliferating within human epithelial cells contains a high proportion of previously unidentified muropeptides (5-10-fold higher than in extracellular bacteria). Amino acid and mass-spectrometry analyses showed that these new components consist of dimeric cross-linked muropeptides lacking one of the two disaccharide (N-acetyl-glucosamine-beta-(1-->4)-N-acetyl-muramic acid) molecules. This unique structure suggests an active role for an N-acetyl-muramyl-L-alanine-amidase in remodelling the peptidoglycan of intracellular S. typhimurium. Additional alterations observed included: (i) the absence of glycine-containing muropeptides; (ii) the increase in the relative proportion of muropeptides cross-linked by L(meso)-diaminopimelyl-D(meso)-diaminopimelic acid (L-D) peptide bridges; and, (iii) the decrease in the global cross-linkage of the macromolecule. The structural alterations observed in the peptidoglycan of intracellular bacteria do not produce loss of the cell envelope. These results show that intracellular residence of S. typhimurium within epithelial cells is accompanied by significant changes in the bacterial cell wall. Remodelling of peptidoglycan structure may constitute another sophisticated strategy of this pathogen for adapting to and colonizing the intracellular niche of eukaryotic cells.

Structural analysis of Bacillus subtilis 168 endospore peptidoglycan and its role during differentiation.

The structure of the endospore cell wall peptidoglycan of Bacillus subtilis has been examined. Spore peptidoglycan was produced by the development of a method based on chemical permeabilization of the spore coats and enzymatic hydrolysis of the peptidoglycan. The resulting muropeptides which were >97% pure were analyzed by reverse-phase high-performance liquid chromatography, amino acid analysis, and mass spectrometry. This revealed that 49% of the muramic acid residues in the glycan backbone were present in the delta-lactam form which occurred predominantly every second muramic acid. The glycosidic bonds adjacent to the muramic acid delta-lactam residues were resistant to the action of muramidases. Of the muramic acid residues, 25.7 and 23.3% were substituted with a tetrapeptide and a single L-alanine, respectively. Only 2% of the muramic acids had tripeptide side chains and may constitute the primordial cell wall, the remainder of the peptidoglycan being spore cortex. The spore peptidoglycan is very loosely cross-linked at only 2.9% of the muramic acid residues, a figure approximately 11-fold less than that of the vegetative cell wall. The peptidoglycan from strain AA110 (dacB) had fivefold-greater cross-linking (14.4%) than the wild type and an altered ratio of muramic acid substituents having 37.0, 46.3, and 12.3% delta-lactam, tetrapeptide, and single L-alanine, respectively. This suggests a role for the DacB protein (penicillin-binding protein 5*) in cortex biosynthesis. The sporulation-specific putative peptidoglycan hydrolase CwlD plays a pivotal role in the establishment of the mature spore cortex structure since strain AA107 (cwlD) has spore peptidoglycan which is completely devoid of muramic acid delta-lactam residues. Despite this drastic change in peptidoglycan structure, the spores are still stable but are unable to germinate. The role of delta-lactam and other spore peptidoglycan structural features in the maintenance of dormancy, heat resistance, and germination is discussed.

Towards a behavioral ecology of ecological landscapes.

Recent developments in landscape-level ecological modeling rest upon poorly understood behavioral phenomena. Surprisingly, these phenomena include animal movement and habitat selection, two areas with a long history of study in behavioral ecology. A major problem in applying traditional behavioral ecology to landscape-level ecological problems is that ecologists and behaviorists work at very different spatial scales. Thus a behavioral ecology of ecological landscapes would strive to overcome this inopportune differential in spatial scales. Such a landscape-conscious behavioral undertaking would not only establish more firmly the link between behavior and ecological systems, but also catalyze the study of basic biological phenomena of Interest to behaviorists and ecologists alike.

Calcium current reactivation after flash photolysis of nifedipine in skeletal muscle fibres of the frog.

1. L-type calcium currents were activated by depolarization of cut muscle fibres of the frog. The current was blocked by the dihydropyridine compound nifedipine (5-10 microM) and reactivated by flash photolysis of the drug. 2. In the presence of nifedipine, increasing the time interval between the onset of depolarization and the flash resulted in progressively faster kinetics of the flash-induced current. This change developed with a slow time course similar to that of normal current activation. 3. A fast gating mode of the normally slow L-type channel was induced by conditioning activation (500 ms prepulses) applied 80 ms before a test step to the same potential. After block by nifedipine, flash-photolysis was carried out 40 ms before the end of the long conditioning pulse. The flash-induced current had the same rapid time course as the current activated by the subsequent test voltage step. 4. Similarly, the time course of current activation was comparable for the voltage-induced fast mode activation (flash applied 5 ms before the test step) and the flash-induced activation 40 ms after the onset of the test depolarization. 5. Our data suggest that in frog skeletal muscle nifedipine inhibits calcium current activation by blocking a rapid channel gating step while the slow conformational change that normally limits the rate of activation of the L-type calcium channel remains unaffected. UV flash illumination results in a fast reactivation indicating that the channels need not be inactivated to be blocked by nifedipine.

A possible role of sarcoplasmic Ca2+ release in modulating the slow Ca2+ current of skeletal muscle.

Ca2+ channels are regulated in a variety of different ways, one of which is modulation by the Ca2+ ion itself. In skeletal muscle, Ca2+ release sites are presumably located in the vicinity of the dihydropyridine-sensitive Ca2+ channel. In this study, we have tried to investigate the effects of Ca2+ release from the sarcoplasmic reticulum on the L-type Ca2+ channel in frog skeletal muscle, using the double Vaseline gap technique. We found an increase in Ca2+ current amplitude on application of caffeine, a well-known potentiator of Ca2+ release. Addition of the fast Ca2+ buffer BAPTA to the intracellular solution led to a gradual decline in Ca2+ current amplitude and eventually caused complete inhibition. Similar observations were made when the muscle fibre was perfused internally with the Ca2+ release channel blocker ruthenium red. The time course of Ca2+ current decline followed closely the increase in ruthenium red concentration. This suggests that Ca2+ release from the sarcoplasmic reticulum is involved in the regulation of L-type Ca2+ channels in frog skeletal muscle.

Modulation of calcium current gating in frog skeletal muscle by conditioning depolarization.

1. Ca2+ inward currents were measured by voltage clamping cut skeletal muscle fibres of the frog (Rana esculenta) in a double-Vaseline-gap system. 2. In order to study the basis of the previously described fast gating mode induced in the Ca2+ inward current by a conditioning depolarization we quantitatively analysed the response to differing features of the conditioning prepulse. 3. The faster activation seen during the second of two depolarizations was confined to the component of the inward current which could be blocked by 5 to 10 microM nifedipine. 4. By applying depolarizing conditioning pulses of gradually increasing length the time course of the transition to the fast gating mode could be determined. 5. Both the transition to the fast gating mode (point 4) caused by a depolarization and the slow inward current activated during the same depolarization showed similar voltage-dependent kinetics. 6. The kinetic change of the test current appeared to be equal when the same fractional activation was achieved at the end of the conditioning pulse independent of its duration or amplitude. 7. Flash photolysis of nifedipine in the interval between conditioning and test pulse showed that the predepolarization causes a rate-enhancing effect even though the slow channels were blocked by nifedipine during the conditioning pulse. 8. We conclude that the transition of the calcium channel from its slow to its fast gating mode is determined by the slow voltage-dependent reaction which limits the rate of channel opening under control conditions. This reaction is apparently not prevented by the binding of nifedipine and the block of current flow through the channel.

Fast gating kinetics of the slow Ca2+ current in cut skeletal muscle fibres of the frog.

1. Calcium currents and intramembrane charge movements were measured in cut twitch muscle fibres of the frog and the time course of activation of the current was studied using various conditioning pulse protocols. 2. When a conditioning activation was produced by a depolarizing pulse which ended before inactivation occurred, a subsequent depolarization led to a faster onset of activation, indicating that the system had not completely returned to the initial state during the interval between the two pulses. 3. The interval between conditioning and test pulse was varied at different subthreshold potentials to study the time course of restoring the steady-state conditions. Complete restoration required a waiting period of about 1 min at the holding potential of -80 mV due to a very slow process but partial recovery was reached within 100 ms. This initial recovery process was strongly voltage dependent and became considerably slower when the interval potential approached the threshold for current activation. 4. Stepping to a roughly 10 mV subthreshold potential without applying a conditioning activation caused no change in the time course of the current produced by a subsequent test depolarization. Depolarizing just to the current threshold caused a slowly progressing acceleration of test current activation. 5. The peak current-voltage relation in the fast gating regime caused by a conditioning activation coincided with the current-voltage relation measured under steady-state conditions, indicating not that a new channel population had become activated but that the same channels showed a different gating behaviour. 6. Intramembrane charge movements measured in 2 mM-Cd2+ and tested at potentials between -40 and +40 mV showed negligible changes when preceded by a strong depolarization. 7. We discuss several possible models which can explain the fact that the current is speeded up by a conditioning activation while the charge movements remain unchanged. It is possible that the fast voltage-dependent transition which becomes visible after conditioning pulses reflects a rapid conformational change of the Ca2+ channel molecule which also occurs during its normal gating mode but remains undetectable in terms of conductance. In view of the hypothesis that the Ca2+ channel molecule forms a voltage sensor for excitation-contraction coupling this fast transition could be coupled to the control of Ca2+ release from the sarcoplasmic reticulum.