Unblock of the slow inward current induces the arrhythmogenic transient inward current in isolated guinea-pig myocytes.
This study investigated whether abrupt changes in extracellular Ca2+ concentration or washout of the Ca2+ antagonists Mn2+ or verapamil, could induce transient inward current (ITI) in enzymatically disaggregated guinea-pig myocytes. Single electrode voltage-clamp techniques were used. ITI was elicited upon repolarization to various voltage steps from an activating step to +20 mV. The holding potential was -80 mV. Slow inward current (ICa) was induced by steps to -10 mV. Continuous exposure to either 2.5 or 6.0 mM Ca2+ did not induce ITI; however, following exposure of cells to 0.5 mM Ca2+ for 20 min which decreased ICa, return to 2.5 or 6.0 mM Ca2+ induced ITI. ITI could be observed for 10 to 20 min following sudden elevations of Ca2+. Similar effects also were seen when Ca2+ was increased from 2.5 to 6.0 mM. Exposure to 2.0 mM Mn2+ or 2.0 microM verapamil blocked ICa. Washout of either blocker induced ITI, particularly in 6.0 mM Ca2+. Peak ITI occurred upon repolarization at c. -70 mV; a reversal potential could not be demonstrated. Thus, abrupt changes in Ca2+ influx, produced either by sudden changes in external Ca2+ or by washout of Ca2+ antagonists, induced ITI with characteristics similar to those described for ITI induced by toxic concentrations of cardiac glycosides.
Cordeiro
J M
JM
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
Howlett
S E
SE
Ferrier
G R
GR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D014700:Verapamil; D002118:Calcium