Effects of pCai and pHi on cell-to-cell coupling

Abstract

Internal longitudinal resistance (ri), a determinant of cardiac conduction, is affected by changes in intracellular calcium and protons. However, the role and mechanism by which H+ and Ca2+ may modulate ri is uncertain. Cable analysis was performed in cardiac Purkinje fibers to measure ri during various interventions. In some experiments, intracellular pH (pHi) was recorded simultaneously to study the pHi-ri relation. Both intracellular Ca2+ and H+ independently modified ri. However, internal resistance of cardiac fibers was insensitive to pHi changes compared to other tissues. A latent period preceded the pHi-related changes in ri and the amount of change depended upon methodology. The results suggest that direct action of protons or ri may be subordinate to other regulatory processes. Ionic regulation of internal longitudinal resistance may occur by more than one mechanism: i) direct cationic binding to sites on junctional membrane proteins; and ii) H+- or Ca2+-dependent phosphorylation of junctional proteins.

The Effect of Acidosis on the Ecg of the Rat Heart

“…Because the duration of the QRS complex reflects the propagation of the action potential through the ventricles, the observation that acidosis has no effect on the duration of the QRS complex suggests that acidosis has little effect on the rate of propagation of the action potential. This is in apparent contrast to previous studies which have reported an increase in intercellular resistance (Reber & Weingart, 1982;Pressler, 1987) and a decrease in the Na¤ current, and hence a decrease in the rate of upstroke of the action potential during acidosis (Kagiyama et al 1982), and a decrease in the rate of conduction of the action potential (Kagiyama et al 1982). However, these effects were reported at more acid pH than those used in the present study.…”

Effect of oxygen withdrawal on active and passive electrical properties of arterially perfused rabbit ventricular muscle.

“…It is in close accordance with measurements of only moderate elevation of intracellular Na + activity 20 in hypoxic myocardium, and with a delayed increase of intracellular calcium in early myocardial ischemia 2425 and during partial metabolic blockade. 26 Recent experiments with isolated Purkinje fibers have shown that the contribution of a decreased intracellular pH to uncoupling is minor, 27 and certainly less than anticipated from previous work. This might explain why the results in ischemia, in which a marked acidosis develops, 28 are not essentially different from myocardial hypoxia, in which acidosis is small.…”

“…It is astonishing that total inhibition of glycolysis or glycogen depletion is required to produce an immediate increase in free intracellular calcium 27 after withdrawal of oxygen. In the absence of complete metabolic blockade, the chemical energy synthesized by anaerobic glycolysis appears to match, for a limited initial period, with a decreased energy demand of the cell.…”

The Protective effect ofd-sotalol against hypoxia-induced myocardial uncoupling

“…The transformation from TVF to SVF is probably induced by suppression of intercellular coupling, caused by prolonged rapid myocardial cell activity [8] and/or VF-induced hypoxia. Hypoxia or ischemia increases junctional resistance, decreases impulse conduction at the gap junctions, and leads to an intercellular uncoupling [9][10], most likely due to an increase in intracellular free Ca 2+ concentration ([Ca2+]i), intracellular acidosis, and/or decrease in intercellular cyclic adenosine monophosphate (cAMP) level ([cAMP]i) [11,12]. Increases in intercellular coupling can transform SVF to TVF by decreasing the number of reentry circles by synchronizing small local circles into bigger ones.…”