Effects of calcium release from sarcoplasmic reticulum on membrane currents in guinea pig atrial cardioballs.
(1) Ca current (ICa) and membrane currents related to Ca-entry during activation of ICa have been studied in cultured atrial myocytes from hearts of adult guinea pigs by means of patch clamp pipettes. The pipettes were filled with solutions containing citrate (65 mM) as major Ca-chelating compound and Cs ions in order to block K currents. (2) In myocytes dialysed with such solutions a monophasic time course of inactivation of ICa is observed, which is 1-2 orders of magnitude slower as compared to studies on intact cardiac cells or cells dialysed with EGTA as only Ca-chelating compound. (3) During long-lasting or repetitive depolarization a second component of ICa inactivation, apart from the slow decay observed in cells dialysed with such solutions, can be seen. This component of inactivation is not related to the depolarization as such but to loading of the cells with Ca2+. Whenever the rapid component of inactivation occurs, a transient inward current (Iti) after repolarization to the holding potential (-40 to -50 mV) is recorded. Both, ICa inactivation and Iti can be mimicked by extracellular application of caffeine (5-10 mM), suggesting both current changes to be caused by a rise in Cai due to Ca release from sarcoplasmic reticulum. In the presence of caffeine the rapid component of ICa-inactivation and Iti are abolished. (4) In addition to ICa inactivation and activation of Iti sarcoplasmic Ca release causes openings of a novel ion channel with large conductance (greater than 200 pS), the function of which is unknown. (5) The results are consistent with the concept of Cai-dependent inactivation of Ca current, which can be caused either by Ca-entry or by Ca-release from the SR. The transient inward current is likely to reflect a process of Ca-removal from the cell, namely Na-Ca exchange.
Lipp
P
P
Department of Cell Physiology, Ruhr-University Bochum, Federal Republic of Germany.
Mechmann
S
S
Pott
L
L
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000166:cytology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D002110:Caffeine; D002118:Calcium