IONIC MECHANISMS OF ACTION-POTENTIAL PROLONGATION AT LOW-TEMPERATURE IN GUINEA-PIG VENTRICULAR MYOCYTES

1. We studied the effects of low temperature on the action potentials and membrane currents of guinea-pig ventricular myocytes, using a tight-seal whole-cell clamp technique. 2. The action potential duration at 95% repolarization was prolonged from 146 +/- 33 ms (mean +/- S.D., n = 6) at 33-34-degrees-C (control temperature) to 314 +/- 83 ms at 24-25-degrees-C (low temperature). 3. In whole-cell clamp experiments, low temperature decreased the calcium current (I(Ca)), the delayed rectifier potassium current (I(K)), and the inwardly rectifying potassium current (I(K1)) with 'apparent' Q10 (temperature coefficient) values of 2.3 +/- 0.6 for I(Ca), 4.4 +/- 1.2 for I(K) tail current and 1.5 +/- 0.3 for I(K1) (n = 7). 4. The effect of low temperature on I(K) was further studied in the presence of 0.6 muM nicardipine to block I(ca). The decay phase of the I(K) tail consisted of two exponential components. The fast but not the slow component was highly sensitive to the temperature change with an apparent Q10 of 4.5. 5. We found that a component of time-independent current is also sensitive to the temperature. The current had a linear I-V relationship, and remained almost unchanged after inhibition of Na+-K+ pump in K+-free external solution. 6. Using our mathematical model of the ventricular action potential (a modification from the DiFrancesco-Noble model), we simulated the action potential at low temperature by modifying some of the membrane currents, namely I(K), I(K1), I(Ca) and a component of background current. It was shown that simultaneous changes in these currents could reproduce approximately 75% of the action prolongation induced by low temperature.