Reoxygenation-induced arrhythmogenic transient inward currents in isolated cells of the guinea-pig heart.
Transient inward currents (Iti), activated by a rise in intracellular Ca concentration, are believed to trigger cardiac arrhythmias in reperfused hearts. In this report, Iti in isolated cardiocytes from the guinea-pig were evoked by reoxygenation following a period of anoxia of between 4 min and 35 min. Reoxygenation was performed 1 min after the full development of an anoxia-induced time-independent K current. This current disappeared within 2-6 s and in the following 10 s Iti developed to maximum amplitude. Iti were evoked using a constant pulse pattern (holding potential Vh = -45 mV; test potential Vt = +10; pulse duration 350 ms; frequency 1 Hz). In more than 95% of the cells, Iti at the holding potential Iti (-45 mV) declined with a time constant of tau = 670 +/- 240 ms (mean +/- SD, n = 17). In two cells, undamped oscillatory currents were observed. The amplitude of Iti (-45 mV) was proportional to the amplitude and duration of the preceding depolarizing test pulse. Test pulses of long duration (500 ms and 1000 ms, mean +/- SD) to potentials positive to +10 mV produced slowly decaying tail currents (tau = 391 +/- 51 ms, mean +/- SD), which superimposed with Iti (-45 mV). The current/voltage relationship of Iti peaked between -30 mV and -10 mV and approximated zero at the most positive potentials, i.e. no reversal of Iti was found up to +80 mV. Using double-pulse protocols (prepulse potential +40 mV), Iti were enhanced at potentials negative to -30 mV and were also present in the range of the normal resting potential of ventricular heart cells. The instantaneous current-voltage relationship was monotone between -50 mV and +40 mV. Because of the dependence of Iti on the preceding depolarization, the instantaneous current-voltage relationship provides more reliable information on the voltage dependence of Iti. The interval between two subsequent Iti (-45 mV) values was 237 +/- 35 ms (mean +/- SD, n = 27) and depended on the amplitude of Iti (-45 mV) to increase by 5.2 +/- 0.5% (mean +/- SD) per 100 pA decrease in Iti (-45 mV). A simple noise analysis showed that if one assumes that ionic channels are responsible for the generation of Iti (-45 mV), their unitary conductance cannot exceed 0.36 pS. We conclude that reoxygenation-induced Iti are triggered by a cyclic release of Ca from the sarcoplasmic reticulum and provide evidence that they are mediated by the electrogenic Na/Ca exchanger.(ABSTRACT TRUNCATED AT 400 WORDS)
Benndorf
K
K
Institut für Vegetative Physiologie, Universität zu Köln, Federal Republic of Germany.
Friedrich
M
M
Hirche
H
H
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D007700:Kinetics; D008564:Membrane Potentials; D015428:Myocardial Reperfusion Injury; D010100:Oxygen / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D015221:Potassium Channels; D019831:Sodium-Calcium Exchanger; D010100:Oxygen; D002118:Calcium