Signal function of potassium channels--clinical aspects.

Potassium (K+) channels are the most diverse class of ion channels, and are important for regulating neuronal excitability and signaling activity in a variety of ways. They are major determinants of membrane excitability, influencing the resting potential of membranes, wave forms and frequencies of action potentials, and thresholds of excitation. Voltage-gated K+ cannels exist not as independent units merely responding to changes in transmembrane potential but as macromolecular complexes able to integrate a plethora of cellular signals that fine tune channel activities. There are a wide variety of therapeutic agents that are targeted to non-K+ channels, but result in unintended block of K+ channels. This K+ channel block can result in potentially serious and sometimes even fatal side effects.

[Modulation of voltage-gated sodium channels by recombinant interferon-alpha2b in the human neuroblastoma cell line IMR-32]. / Moduliatsiia potentsiialupravliaemykh natrievykh kanalov kletok neiroblastomy cheloveka IMR-32 pri deistvii rekombinantnogo interferona-alfa2b.

Clonal human neuroblastoma cells imr-32 are a suitable model system for studies of neuronal excitability modulation. The ability interferon-alpha 2b "laferon" to modulate the mechanisms of electrical activity was studied in whole-cell patch-clamped undifferentiated human neuroblastoma cells IMR-32. It was shown that 1 h incubation of IMR-32 cells at 37 degrees C in medium with laferon (600 U/ml) exerted changes in voltage-dependent properties of Na(+)-channels. The results of the present study demonstrate that laferon decreased of Na(+)-channels sensitivity to changes of membrane potential leading of IMR-32 cells electrical excitability decrease.

Effects of temperature and Na0+ on the relaxation of phasic and tonic tension of guinea-pig ureter muscle.

Effects of temperature and Na0+ on the relaxation of guinea-pig ureter smooth muscle were studied. Relaxation of phasic contraction was found to be highly temperature-dependent, practically independent of Na0+ and Ca02+, and resistant to vanadate. The relaxation of the tonic tension of both high-K and low-Na contracture was less temperature-dependent and affected by Na0+. The relaxation of tonic tension produced by introduction of Na0+ was about 3-5 times faster than that produced by Ca-free solution. La3+ ions were found to block the relaxation of the tonic component of the Na+-free contracture initiated by removal of Ca02+. Three systems of regulation of cell calcium are suggested to be operative in the ureter muscle: a fast one which is highly temperature-dependent and responsible for the relaxation of the phasic contraction (probably the sarcoplasmic reticulum), and two slow membrane-linked carriers, one of which is dependent on Na0+ (probably Na-Ca exchange) and another one which is independent of Na0+ and inhibited by La3+ (probably Ca-pump).

Effects of caffeine on the electrical and mechanical activity of guinea-pig ureter smooth muscle.

The effects of caffeine on the electrical and mechanical activity of the guinea-pig ureter smooth muscle were studied. Under untreated conditions caffeine mainly showed inhibitory action on the ureter, inhibiting the evoked action potentials and phasic contractions as well as potassium contracture. Caffeine was also found to suppress the low-Na contracture of Na-loaded ureter muscle. It is established that Na-loaded tissue is able to generate transient contracture in response to caffeine application at 37 degrees C. These caffeine contractures could be evoked under completely removed [Ca2+]0 and in the presence of high doses of Ca-channel blockers (nifedipine, diltiazem, Mn ions) and could be reversibly blocked by tetracaine, procaine and benzocaine. Caffeine contractures could also be produced by the ureter muscle placed in isotonic K-solution. Cooling significantly potentiated low-Na, potassium and caffeine contractures of the ureter muscle. Filling of the store is totally dependent on the entry of Ca ions from the extracellular Ca2+ store sites which sequester Ca ions entering the cell on either Na-Ca exchange or via voltage operated Ca channels.

The effects of local anaesthetics on the electrical and mechanical activity of the guinea-pig ureter.

The effects of local anaesthetic tertiary amines (procaine, lignocaine and tetracaine) as well as neutral (benzocaine) and permanently charged (QX-314) local anaesthetics were studied on the evoked electrical and mechanical activity of the ureter smooth muscle. 'Low' concentrations of procaine and lignocaine (0.1-1mM) at pH 7.4 increased the duration of the slow plateau component of the evoked action potentials. The amplitude of the phasic contraction was consequently increased within the first 5 min of exposure. Tetracaine 0.1 mM caused a transient increase in the duration of the plateau and amplitude of the phasic contraction within the first 1-2 min only. The stimulant action of the local anaesthetics was greatly reduced in the presence of tetraethylammonium (TEA). All the tertiary local anaesthetics caused depolarization of the membrane accompanied by an increase in the size of the electronic potentials. Lignocaine normally initiated the discharge of spontaneous action potentials. High concentrations of lignocaine (5 mM) and tetracaine (0.5 mM) caused complete inhibition of the evoked action potentials and phasic contractions. Procaine 5 mM predominantly inhibited the contractile responses. The permanently charged local anaesthetic QX-314 (1 mM) caused an increase in the duration and amplitude of the plateau, increasing the number of spikes and the amplitude and duration of the phasic contraction. It also depolarized the ureter smooth muscle cells increasing the size of electronic potentials. The neutral local anaesthetic benzocaine at 1 mM caused a reversible selective blockade of the plateau component of the evoked action potential and a gradual reduction in the amplitude of the phasic contraction. No change in either the membrane potential or the membrane conductance was observed. 7 High pH. (pH 9) significantly increased while low pH0 (pH 6) decreased the inhibitory action of procaine and lignocaine but did not alter the effects of benzocaine and QX-314. 8 Benzocaine caused a relaxation of the high-K-induced contraction, preferentially blocking the tonic component, whereas QX-314 had no effect on the KC1-contracture of the ureter muscle. 9 Two sites of action in the ureter smooth muscle cell membrane for local anaesthetics are suggested. One site interacts with local anaesthetics in a charged form, while the other one interacts with those in a lipid-soluble neutral form. The charged form of local anaesthetics has a TEA-like action, while the neutral form predominantly causes blockade of 'slow' Na/Ca channels.

[Electroregulated potassium channels of the somatic membrane of mollusk neuron membranes]. / Elektroupravliaemye kalievye kanaly somaticheskoi membrany neironov molliuskov.

The delayed potassium current in mollusc neurons was separated into two components: a noninactivating component and a transient (inactivating) component. A noninactivating potassium current is not affected by changes in temperature, whereas an inactivating component decreases substantially under cooling. Internal Na+ can block the delayed outward potassium current. The blockade of the inactivating potassium current is strongly voltage-dependent. The voltage dependence of the blockade of the noninactivating potassium current is not so clear. These results are consistent with the hypothesis that there are two forms of the delayed potassium current channel. The effect of temperature and internal Na+ on the fast outward current is similar to that on the inactivating component of the delayed potassium current.

[Thermodynamic characteristics of the gating mechanisms of fast potassium channels of somatic membranes of snail neurons]. / Thermodinamicheskie kharakteristiki vorotnykh mekhanizmov bystrykh kalievykh kanalov somaticheskoi membrany neironov ulitki.

The fast potassium current conductance was treated as a system obeying n3 kinetics. The steady-state arrangement of the gating charges have been analyzed in terms of a Boltzmann distribution with two allowed configurations. Rate equations were obtained using the transition rate theory and assuming that each reaction was rate limited by only one energy barrier. These equations gave a simple exponential function for the voltage dependence of the rates. The single-barrier equations were used to estimate the energies of formation of the transition state.

[Effect of the alkaloid lappaconitine on ion currents through the somatic membrane of Helix pomatia neurons]. / Vliianie alkaloida lappakonitina na ionnye toki cherez somaticheskuiu membranu neironov Helix pomatia.

The effect of alkoloid lappaconitine on ionic currents through the somatic membrane of identified neurons of the mollusc Helix pomatia was studied under voltage-clamp conditions. It is shown that 4 mM lappaconitine causes a reversible blocking action on the calcium channels. Concentration exceeding 4 mM causes irreversible changes. Lappaconitine had either an insignificant or no effect on sodium currents.