ISSN:
1432-2013
Keywords:
Isolated cardiocytes
;
Transient inward current
;
Current-voltage relationship
;
Kinetics
;
Na/Ca exchanger
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Transient inward currents (I ti), activated by a rise in intracellular Ca concentration, are believed to trigger cardiac arrhythmias in reperfused hearts. In this report, I ti 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 I ti developed to maximum amplitude. I ti were evoked using a constant pulse pattern (holding potential V h=−45 mV; test potential V t=+10 mV; pulse duration 350 ms; frequency 1 Hz). In more than 95% of the cells, I ti at the holding potential I ti (−45 mV) declined with a time constant of τ=670±240 ms (mean±SD, n=17). In two cells, undamped oscillatory currents were observed. The amplitude of I ti (-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 (τ=391±51 ms, mean ± SD), which superimposed with I ti (−45 mV). The current/voltage relationship of I ti peaked between −30 mV and −10 mV and approximated zero at the most positive potentials, i.e. no reversal of I ti was found up to +80 mV. Using double-pulse protocols (prepulse potential +40 mV), I ti 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 I ti on the preceding depolarization, the instantaneous current-voltage relationship provides more reliable information on the voltage dependence of I ti. The interval between two subsequent I ti (−45 mV) values was 237±35 ms (mean ± SD, n=27) and depended on the amplitude of I ti (−45 mV) to increase by 5.2±0.5% (mean ± SD) per 100 pA decrease in I ti (−45 mV). A simple noise analysis showed that if one assumes that ionic channels are responsible for the generation of I ti (−45 mV), their unitary conductance cannot exceed 0.36 pS. We conclude that reoxygenation-induced I ti 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. The arrhythmogenic potency of reoxygenation-induced I ti is demonstrated under current-clamp conditions.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00370523
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