Different action of ethosuximide on low- and high-threshold calcium currents in rat sensory neurons.

The effects of ethosuximide on calcium channels were studied on dorsal root ganglion neurons from one-day-old rats using the patch-clamp technique. Bath application of ethosuximide induced dose-dependent and reversible suppression of calcium currents without affecting their time-course. Substantial differences between the effects of ethosuximide on the low-threshold and high-threshold (T- and L-) currents were observed. Ethosuximide reduced the T-current with greater potency than the L-current (Kd for T-current is 7 microM vs 15 microM for L-current). This relative specificity of its action still remained if applied at concentrations up to 1 mM. These data support the hypothesis according to which the anti-epileptic action of ethosuximide is related to reduction of the low-threshold calcium currents in sensory neurons.

The effect of permeant ions on single calcium channel activation in mouse neuroblastoma cells: ion-channel interaction.

1. Single low-threshold inactivating (LTI or T-type) Ca2+ channels of undifferentiated neuroblastoma cells (clone N1E-115) were investigated using the patch-clamp technique. 2. Single-channel conductance, gi, for Ca2+, Sr2+ or Ba2+ as a permeant cation was similar (7.2 pS). Mean channel open time, tau op, was also practically independent of the divalent ion species; it decreased from 0.7 to 0.3 ms between -40 and 0 mV. 3. Modification of the calcium channel selectivity by lowering the external Ca2+ concentration to 10(-8) M produced an increase in gi for Na+ and Li+ ions and a shift of potential-dependent characteristics in the hyperpolarizing direction. Voltage sensitivity and absolute values of tau op were also changed. These changes were dependent on both permeant monovalent ion type and concentration. 4. At high [Na+]o, tau op was almost potential independent (congruent to 0.3 ms). Decrease in [Na+]o and substitution of Li+ for Na+ increased tau op and the steepness of its potential dependency. 5. The divalent and monovalent cations that were tested had much smaller effect on the mean intraburst shut time, tau cl(f), which was nearly independent of membrane potential (congruent to 0.6 ms). By contrast, mean burst duration was strongly potential dependent and noticeably affected by permeant ion type. 6. All kinetic changes were analysed in terms of a four-state sequential model for channel activation. According to this model the channel enters the open state through three closed states. Transitions between closed states can be formally related to the transmembrane movement of two charged gating particles (m2 process). The interaction between ion flux and a sterical region of the Ca2+ channel selectivity filter may, depending on ion transfer rate and ionic radius, lead to a local increase of the dielectric constant, resulting in redistribution of the electric field and changes in potential dependency of tau op.

[Ultrastructural analysis of myocardial condition during cardioplegic protection in heart valve prosthesis]. / Ul'trastrukturnyi analiz sostoianiia miokarda v usloviiakh kardioplegicheskoi zashchity pri protezirovanii klapanov serdtsa.

The article deals with the results of ultrastructural study of the myocardium at three stages of cardiosurgical operations: preischemic, ischemic, and during reoxygenation. A statistically significant difference was revealed in the condition of the cardiomyocyte organelles in each of these stages, and the degree of their intraoperative destruction was determined. It is concluded that ischemia of more than 90 minutes redoubles the progress of irreparable changes of the cardiomyocytes, particularly in patients with severe damage to the myocardium in the preischemic stage. The search for means of cardioprotection for these patients must be continued.

[The characteristics of the sodium currents across EGTA-modified calcium channels in the membrane of cultured rat cardiomyocytes]. / Kharakteristika natrievykh tokov cherez EGTA-modifitsirovannye kal'tsievye kanaly membrany kul'tiviruemykh kardiomiotsitov krys.

In isolated, cultured neonatal rat ventricular myocytes sodium currents through calcium channels induced by lowering of extracellular calcium concentration 100 nmol/l have been investigated by whole-cell patch clamp technique. Such Na(+)-carried currents are modulated by classic Ca2+ agonists and antagonists. The potential-dependent characteristics of Na+ current are shifted at 20 mV in hyperpolarizing direction as compared to initial Ca(2+)-carried current. The inactivation decay of Na+ current through Ca2+ channels has the monoexponential behaviour. The possible action of extracellular Ca2+ lowering on Ca2+ channel selective filter and gating mechanisms is suggested.

[Lack of low-threshold calcium channels in the membrane of cultured cells of the heart ventricle of newborn rats]. / Otsutstvie nizkoporogovykh kal'tsievykh kanalov b membrane kul'tiviruemykh kletok zheludochka serdtsa novorozhdennykh krys.

In isolated, cultured neonatal rat ventricular myocytes calcium current was investigated by whole-cell patch clamp technique. The shift of holding potential values from -100-80 mV to -40 mV caused no significant changes in calcium current potential-dependent and kinetic properties. No calcium current component with preferential steady-state inactivation at membrane potentials ranged between -100 and -60 mV was observed. Calcium current component resistant to classic Ca-antagonists action was not found either. All data listed above permit a conclusion on lack of the low-threshold calcium channels in the membrane of single cultured neonatal rat ventricular myocytes. Possible reasons of the absence of this type of calcium are discussed.

[2 components of the high-threshold calcium current possessing different sensitivities to omega-conotoxin in the membrane of pheochromocytoma cells]. / Dva komponenta vysokoporogovogo kal'tsievogo toka, obladaiushchie raznoi chuvstvitel'nost'iu k omega-konotoksinu, v membrane kletok feokhromotsitomy.

Blockade of the high-threshold calcium currents by omega-conotoxin (CgTx) was investigated by patch-clamp recordings of whole-cell currents in cultured cells of pheochromocytoma PC12. CgTx (10 mumol/l) preferentially blocked only a steady-state component of the calcium current. Inactivated component was insensitive to CgTx (up to 50 mumol/l concentration). The two component nature of the high-threshold calcium current in pheochromocytoma PC12 cells was suggested.

[Diagnosis of critical stenosis of the coronary arteries in patients with ischemic heart disease]. / Diagnostika kriticheskogo stenoza koronarnykh arterii u bo'lnykh ishemicheskoi bolez'niu serdtsa.

Possible diagnosis of critical coronary stenosis using a bicycle ergometry along with coronary angiography was studied in 193 patients. Informative hemodynamic criteria were proposed for noninvasive diagnosis of anatomic critical coronary stenosis during exercise. Application of coronary angiography combined with a bicycle ergometric testing enabled the true critical coronary stenosis to be diagnosed.

[Immediate hemodynamic effect of sequential atrioventricular pacing in cardiosurgical patients]. / Neposredstvennyi gemodinamicheskii éffekt posledovatel'noi predserdno-zheludochkovoi élektrokardiostimuliatsii u kardiokhirurgicheskikh bol'nykh.

The results of ventricular, atrial and sequential atrioventricular pacing, conducted in 16 cases of open-heart surgery, demonstrated that sequential atrioventricular pacing produced the best hemodynamic effect owing to the optimization of atrioventricular delay and impulse frequency.

[Incidence and characteristics of lesions of extracranial segments of the brachiocephalic arteries in patients with ischemic heart disease]. / Chastota i osobennosti porazhenii ékstrakranial'nykh otdelov brakhitsefal'nykh arterii u bol'nykh ishemicheskoi bolezn'iu serdtsa.

The results of investigation are reviewed in 563 patients with angiographically-confirmed coronary arterial lesions. Combined affection of coronary and brachiocephalic arteries was recorded in 106 (18.8%) patients with isolated lesions of brain-supplying arteries in 59 and multiple lesions in 47. The incidence of the affection of brachiocephalic arteries increases with the involvement of the coronary bed, being 6.6% where one coronary artery is affected, 18.8% for two, and 23.0% for three affected coronary arteries. Ultrasonic dopplerography is of particular value for these patients as the most informative noninvasive procedure for the investigation of brachiocephalic arteries.

Three types of calcium channels in the membrane of mouse sensory neurons.

Three types of electrically-operated calcium channels have been identified in the membrane of cultured dorsal root ganglion neurons from mouse embryos using patch clamp technique. Low-threshold inactivating (LTI) channels with the lowest unitary conductance (5.7 pS with 60 mM Sr2+ or 7.2 pS with 60 mM Ba2+) preserved their activity for a long time on excised membrane patches and were insensitive to dihydropyridine Ca channel agonist Bay K8644. Corresponding whole-cell current could be decreased by 40% with 25 microM D-600. High-threshold inactivating (HTI) channels had somewhat higher unitary conductance (7 pS and 11.4 pS for Sr2+ or Ba2+ at 60 mM concentration) and were much more dependent upon intracellular metabolic support. D-600 inhibited the corresponding HTI whole-cell current by about 10%. High-threshold non-inactivating (HTN) channels were the most conducting ones (9 pS and 18.4 pS for 60 mM Sr2+ or 60 mM Ba2+) and their functioning was strongly metabolic dependent. Whole-cell HTN current could be slightly enhanced by 10 microM Bay K8644 due to some prolongation of channel mean open time. Effect of Bay K8644 was much less pronounced than that reported for cardiac cells. HTN whole-cell current could be almost completely blocked by 25 microM D-600. The described three types of calcium channels revealed different potential dependence and absolute values of mean channel open time.

[Left ventricular contractility in bioprosthesis of the heart valves]. / Sokratimost' levogo zheludochka pri bioprotezirovanii klapanov serdtsa.

An assessment of pre- and post-operative left ventricular function has demonstrated that initial hemodynamic conditions of the defect should be taken into account in combined evaluation of preoperative general condition of the patient and the choice of the prosthesis. At the same time, the pattern of change may be used as an indicator of the adequacy of defect correction and prosthetic implant function.

[Single channels of low and high-threshold calcium channels of the membrane of sensory neurons in the mouse]. / Odinichnye kanaly nizko- i vysokoporogovykh kal'tsievykh tokov membrany sensornykh neironov myshi.

Single calcium channels of cultured dorsal root ganglion cells from mouse embryos were studied using patch clamp method in its cell-attached configuration. Two types of activity of unitary calcium channels were found. The first one which arose at membrane potentials near--50-40 mV was characterized by unitary current amplitude of 0.37 +/- 0.04 pA with 40 mmol/l Ca2+ in the pipette solution, mean open time of 0.6 ms and intraburst mean shut time of 1.2 ms. It displayed voltage- and time-dependent inactivation. The corresponding values for the second one which required much more positive depolarization to be activated (approximately 0 mV) and did not express noticeable inactivation were: 0.53 +/- 0.04 pA, 0.8 ms and 0.8 ms. It is concluded that the recorded types of unitary activity are associated respectively with low- and high-threshold calcium currents which have been found earlier while studying whole cell currents.

[Evaluation of the early signs of left ventricular failure using bipolar chest rheography]. / Otsenka rannikh priznakov nedostatochnosti levogo zheludochka s pomoshch'iu bipoliarnoi grudnoi reografii.

The comparison of findings obtained with bipolar chest rheography with radiologic evidence of hypervolemia in the pulmonary circulation and left-ventricular end-diastolic pressure in 90 coronary patients has suggested that the basal impedance index (the ratio of estimated to actual basal impedance values) can be measured as it corresponds to the severity of pulmonary congestion. The basal impedance index values below 6.10(-2) signal congestive left-ventricular failure.

[Single calcium channels of spinal ganglion neurons in the rat]. / Odinochnye kal'tsievye kanaly neironov spinal'nykh gangliev krys.

Single calcium channels in isolated dorsal root ganglion cells of the newborn rat were studied using the method of patch clamp in its cell-attached configuration. With 60 mmol/l of Ca2+ in the pipette (extracellular) solution, the amplitude of unitary Ca currents varied from 0.58 +/- 0.05 pA to 0.43 +/- 0.05 pA with a 20 mV change of the potential, which corresponds to a channel conductance of 7 +/- 0.5 pS. The distribution of the open time was monoexponential with the time constant of 0.75 ms not depending on the membrane potential. The distribution of closed time approached a biexponential time course. The fast component (approximately 0.8 ms) showed no dependence on the membrane potential, while the time constant of the slow one decreased with increasing depolarization (from 22 ms to 4 ms with a 20 mV change of the potential). Using experimentally obtained time parameters which describe single calcium channel function and assuming a three-state model of the channel, the numerical values of the rate constants of transitions between individual states were determined.