Calcium extrusion during aftercontractions in cardiac myocytes: the role of the sodium-calcium exchanger in the generation of the transient inward current.
Spontaneous release of calcium from the sarcoplasmic reticulum leads to delayed afterdepolarizations which may represent an arrhythmogenic mechanism in the intact heart. The current underlying delayed afterdepolarizations is the transient inward current, but how this is triggered by a spontaneous rise in cytoplasmic calcium concentration is a matter of debate. We have investigated this by rapid application of caffeine to isolated guinea-pig cardiac myocytes, before and after drive train-induced aftercontractions. Mean (+/- s.e.m.) sarcoplasmic reticulum content reduced from 85 +/- 11 micromol/l accessible cell volume to 53 +/- 9 micromol/l accessible cell volume (n=11) during the course of the aftercontraction. The charge movement expected to result from extrusion of this calcium via the sodium-calcium exchanger was 70.1 +/- 5.4 pC, compared with charge measured during the transient inward current of 70.1 +/- 10.8 pC in the same cells (P=0.9969). Rapid inhibition of the sodium-calcium exchanger, by replacement of the superfusate with a sodium and calcium free solution between the end of the drive train and the aftercontraction, completely abolished the transient inward current (from 90.4 +/- 10.2 pA inward current to 23.8 +/- 14.9 pA outward current, P<0.001). We conclude that the transient inward current in this species is explained entirely by sodium-calcium exchange current without the need to invoke other calcium-activated conductances.
Egdell
R M
RM
National Heart & Lung Institute, London, UK.
MacLeod
K T
KT
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D002478:Cells, Cultured; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology*
D002413:Cations, Divalent; D019831:Sodium-Calcium Exchanger; D002118:Calcium