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S S Sheu

Publications and source records attributed to S S Sheu.

60 records · Page 4Linked to original sources

The resting potential in heart muscle.

The resting potential in heart muscle is largely a K+ diffusion potential as predicted by Bernstein. However, deviations from the Nernst equation are reported which could be the result of different intracellular and extracellular activity coefficients, errors in measurement of intracellular K+, partial permeabilities to other ions, or electrogenic pumps. The origin of the cardiac resting potential was investigated by use of K+- and Na+-selective microelectrodes during exposure of ventricular muscle and Purkinje fibers to various solutions. The intracellular activity coefficient for K+ was apparently less than the extracellular one, and membrane potential in ventricular muscle followed the K+ activity gradient for extracellular K+ of 10 mM or more. In Purkinje fibers, the resting potential correlated directly with intracellular K+ activity and inversely with intracellular Na+ activity. At normal and low extracellular K+, there is a substantial Na+ leakage and some Ca2+ leakage. No contribution of electrogenic pumps or extracellular K+ accumulation could be found in the steady resting state.

Animals↗

Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development.

Na+- and CA2+-sensitive microelectrodes were used to measure intracellular Na+ and Ca2+ activities (alpha iCa) of sheep ventricular muscle and Purkinje strands to study the interrelationship between Na+ and Ca2+ electrochemical gradients (delta muNa and delta muCa) under various conditions. In ventricular muscle, alpha iNa was 6.4 +/- 1.2 mM and alpha iCa was 87 +/- 20 nM ([Ca/+] = 272 nM). A graded decrease of external Na+ activity (alpha oNa) resulted in decrease of alpha iNa, and increase of alpha iCa. There was increase of twitch tension in low-alpha oNa solutions, and occasional increase of resting tension in 40% alpha oNa. Increase of external Ca2+ (alpha oCa) resulted in increase of alpha iCa and decrease of alpha iNa. Decrease of alpha oCa resulted in decrease of alpha iCa and increase of alpha iNa. The apparent resting Na-Ca energy ratio (delta muCa/delta muNa) was between 2.43 and 2.63. When the membrane potential (Vm) was depolarized by 50 mM K+ in ventricular muscle, Vm depolarized by 50 mV, alpha iNa decreased, and alpha iCa increased, with the development of a contracture. The apparent energy coupling ratio did not change with depolarization. 5 x 10(-6) M ouabain induced a large increase in alpha iNa ad alpha iCa, accompanied by an increase in twitch and resting tension. Under the conditions we have studied, delta muNa and delta muCa appeared to be coupled and n was nearly constant at 2.5, as would be expected if the Na-Ca exchange system was able to set the steady level of alpha iCa. Tension threshold was about 230 nM alpha iCa. The magnitude of twitch tension was directly related to alpha iCa.

Animals↗

Changes in intracellular Ca2+ activity with stimulation in sheep cardiac Purkinje strands.

One hypothesis to explain increased contraction strength with increased stimulation rate in heart muscle requires that stimulation increase intracellular Na+ activity(aiNa). This is proposed to increase intracellular Ca2+ activity (aiCa) via the Na-Ca exchange mechanism. Several indirect studies have supported the idea that aiNa is increased with stimulation, and more recently we have directly demonstrated aiNa elevation with Na+-sensitive microelectrodes. We now report aiCa to be elevated after trains of stimuli at different rates in sheep cardiac Purkinje strands. The resting level of aiCa in six strands was 93 +/- 15 (SE) nM, and it increased to 162 +/- 20 nM after stimulation at 3 Hz. The recovery of aiCa was exponential, and the time constants of 80-120 s were similar to those previously found for aiNa. A positive force-frequency relation was found in sheep Purkinje fibers that correlated with the increased aiCa. The results support the hypothesis that the Na-Ca exchange system plays an important role in the force-frequency phenomenon.

Animals↗

Increase in intracellular sodium ion activity during stimulation in mammalian cardiac muscle.

Changes in stimulation rate alter the electrical and mechanical characteristics of myocardial cells. We have investigated the possibility that intracellular sodium activity (aiNa) changes with stimulation and correlates with changes in contraction strength. Two kinds of liquid membrane Na+-selective microelectrodes were used to measure aiNa in guinea pig and sheep ventricular muscle and in sheep Purkinje strands. Stimulation produced a rate- and time-dependent elevation of aiNa. Small increases in aiNa were seen at stimulation rates as slow as 0.2 Hz, and faster rates of stimulation elevated aiNa by over 30%. The changes seen in Purkinje strands and ventricular muscle were similar. Following a period of stimulation, aiNa and Vm returned to their pre-stimulus levels with the same time courses. This is consistent with the suggestion that the post-stimulation hyperpolarization is the result of an increased rate of electrogenic Na+ extrusion. The effects of stimulation on aiNa and tension were compared with those of ouabain. The comparison suggests that rapid stimulation could produce increased contraction strength as the result of a substantial gain in intracellular calcium via a Na-Ca exchange mechanism, but that this is only one of several factors determining the force-frequency relationship.

Animals↗

Intracellular potassium and sodium activities of chick ventricular muscle during embryonic development.

1. The basis of the resting potential of chick embryo ventricular muscle was studied by use of ion-selective micro-electrodes. Membrane resting potential hyperpolarized from -65 . 4 +/- 1 . 1 mV (mean +/- S.E.) at age 4 day to -75 . 8 +/- 0 . 6 mV at age 18 day. Action potential overshoot increased from +19 . 8 +/- 0 . 9 at age 4 day to +33 . 1 +/- 0 . 6 mV at age 18 day. 2. Intracellular K+ activity measured with ion-selective micro-electrodes increased from 71 . 3 +/- 1 . 9 mM at age 4 day to 89 . 9 +/- 1 . 1 at age 18 day. Intracellular Na+ activity decreased from 12 . 5 +/- 0 . 4 to 7 . 0 +/- 0 . 3 mM during the same period. The difference between membrane resting potential and the calculated potassium equilibrium potential decreased with development. PNa/PK estimated from the constant field equation decreased from 0 . 012 at age 4 day to 0 . 005 at age 18 day. 3. The hyperpolarization of resting potential and the increased action potential overshoot during development could be explained by a rise in intracellular K+ activity and a fall in intracellular Na+ activity, as if the Na--K exchange pump became more active.

Action Potentials↗

Intra- and extracellular K+ and Na+ activities and resting membrane potential in sheep cardiac purkinje strands.

K+- and Na+-selective liquid ion-exchanger microelectrodes were used to measure intracellular K+ activity (aK i) and intracellular Na+ activity (aNa i) of sheep cardiac Purkinje strands in different solutions. In Tyrode's solution with an extracellular K+ concentration ([K+]o) of 5.4 mM, aK i was between 80 and 140 mM and averaged 109.6 +/- 4.0 mM (mean +/- SE, 20 strands). The measured aK i was closely correlated with the resting membrane potential, so that the K+ equilibrium potential was always about 10 mV more negative. When [K+]o was lower than 5.4 mM, aK i fell, and when [K+]o was higher than 5.4 mM it increased, aNa i was between 4 and 12 mM, and averaged 6.6 +/- 0.6 mM (14 strands). Its variation was also correlated with resting potential. Over a wide range of [K+]o and extracellular Na+ concentrations ([Na+]o), the aiNa changes were such that Na+ equilibrium potential remained between +70 and +80 mV. The quiescent membrane behaved as a K+-electrode when [K+]o was higher than 5.4 mM. When [K+]o was low and [Na+]o was zero, then Ca2+ and perhaps Cl- contributed to the resting potential.

Animals↗