Biomedical subjects

G E Kirsch

Publications and source records attributed to G E Kirsch.

58 records · Page 4Linked to original sources

PubMed1980

Interaction of n-alkylguanidines with the sodium channels of squid axon membrane.

The effects of n-alkylguanidine derivatives on sodium channel conductance were measured in voltage clamped, internally perfused squid giant axons. After destruction of the sodium inactivation mechanism by internal pronase treatment, internal application of n-amylguanidine (0.5 mM) or n-octylguanidine (0.03 mM) caused a time-dependent block of sodium channels. No time-dependent block was observed with shorter chain derivatives. No change in the rising phase of sodium current was seen and the block of steady-state sodium current was independent of the membrane potential. In axons with intact sodium inactivation, an apparent facilitation of inactivation was observed after application of either n-amylguanidine or n-octylguanidine. These results can be explained by a model in which alkylguanidines enter and occlude open sodium channels from inside the membrane with voltage-independent rate constants. Alkylguanidine block bears a close resemblance to natural sodium inactivation. This might be explained by the fact that alkylguanidines are related to arginine, which has a guanidino group and is thought to be an essential amino acid in the molecular mechanism of sodium inactivation. A strong correlation between alkyl chain length and blocking potency was found, suggesting that a hydrophobic binding site exists near the inner mouth of the sodium channel.

Animals↗

PubMed1978

3,4-diaminopyridine. A potent new potassium channel blocker.

3,4-diaminopyridine has been found to act very potently in selectively blocking the potassium channels of squid axon membranes. The apparent dissociation constants for this action are estimated to be 5.8 micron and 0.7 micron for external and internal applications, respectively, the potency being about 50 times higher than that of 4-aminopyridine. The block depends upon the membrane potential, time, and stimulus frequency. 3,4-diaminopyridine shows great promise as a useful tool for the study of membrane ionic channels.

Action Potentials↗

PubMed1978

Latency-relaxation in single muscle fibres.

1. Latency relaxation and twitch tension were recorded simultaneously in single isolated muscle fibres of Xenopus laevis. 2. During low frequency (0.6 or 1 pulse/sec) repetitive stimulation, three successive phases of twitch tension were observed: negative staricase (a slight drop in tension), positive staircase (about 15% increase in tension) and fatigue. At the same time the amplitude of latency relaxation decreased monotonically, and near the peak of positive staircase, the amplitude decreased almost to an undetectable level. 3. The application of caffeine (0.1--1.5 mM) increased peak twitch tension by 15--200%, but decreased the latency relaxation amplitude by 30--93%. 4. The application of Ca-release inhibitors, deuterium oxide and dantrolene sodium, caused a 43--89% decline in peak twitch tension but no change in latency relaxation amplitude. 5. The lack of correlation between changes in peak twitch tension and latency relaxation amplitude suggests that latency relaxation is associated with the mechanism which triggers Ca2+ relase rather than with Ca2+ release itself.

Animals↗

PubMed1977

Delayed rectification in the transverse tubules: origin of the late after-potential in frog skeletal muscle.

Tetanic stimulation of skeletal muscle fibers elicits a train of spikes followed by a long-lasting depolarization called the late after-potential (LAP). We have conducted experiments to determine the origin of the LAP. Isolated single muscle fibers were treated with a high potassium solution (5 mM or 10 mM K) followed by a sudden reduction of potassium concentration to 2.5 mM. This procedure produced a slow repolarization (K repolarization), which reflects a diffusional outflow of potassium from inside the lumen of the transverse tubular system (T system). Tetanic stimulation was then applied to the same fiber and the LAP was recorded. The time courses of K repolarization and LAP decay were compared and found to be roughly the same. This approximate equality held under various conditions that changed the time courses of both events over a wide range. Both K repolarization and the LAP became slower as fiber radius increased. These results suggest that LAP decay and K repolarization represent the same process. Thus, we conclude that the LAP is caused by potassium accumulation in the T system. A consequence of this conclusion is that delayed rectification channels exist in the T system. A rough estimation suggests that the density of delayed rectification channels is less in the T system than in the surface membrane.

Action Potentials↗