| 10873555 |
Bertaso F, Hendry BM, Donohoe P, James AF: Alterations in outward K (+) currents on removal of external Ca (2+) in human atrial myocytes. Biochem Biophys Res Commun. 2000 Jun 24;273(1):10-6.
External divalent cations are known to play an important role in the function of voltage-gated ion channels. The purpose of this study was to examine the sensitivity of the voltage-gated K (+) currents of human atrial myocytes to external Ca (2+) ions. Myocytes were isolated by collagenase digestion of atrial appendages taken from patients undergoing coronary artery-bypass surgery. Currents were recorded from single isolated myocytes at 37 degrees C using the whole-cell patch-clamp technique. With 0.5 mM external Ca (2+), voltage pulses positive to -20 mV (holding potential = -60 mV) activated outward currents which very rapidly reached a peak (I (peak)) and subsequently inactivated (tau = 7.5 +/- 0.7 msec at +60 mV) to a sustained level, demonstrating the contribution of both rapidly inactivating transient (I (to1)) and non-inactivating sustained (I (so)) outward currents. The I (to1) component of I (peak), but not I (so), showed voltage-dependent inactivation using 100 msec prepulses (V (1/2) = -35.2 +/- 0.5 mV). The K (+) channel blocker, 4-aminopyridine (4-AP, 2 mM), inhibited I (to1) by approximately 76% and reduced I (so) by approximately 33%. Removal of external Ca (2+) had several effects: (i) I (peak) was reduced in a manner consistent with an approximately 13 mV shift to negative voltages in the voltage-dependent inactivation of I (to1). (ii) I (so) was increased over the entire voltage range and this was associated with an increase in a non-inactivating 4-AP-sensitive current. (iii) In 79% cells (11/14), a slowly inactivating component was revealed such that the time-dependent inactivation was described by a double exponential time course (tau (1) = 7.0 +/- 0.7, tau (2) = 90 +/- 21 msec at +60 mV) with no effect on the fast time constant. Removal of external Ca (2+) was associated with an additional component to the voltage-dependent inactivation of I (peak) and I (so) (V (1/2) = -20.5 +/- 1.5 mV). The slowly inactivating component was seen only in the absence of external Ca (2+) ions and was insensitive to 4-AP (2 mM). Experiments with Cs (+)-rich pipette solutions suggested that the Ca (2+)-sensitive currents were carried predominantly by K (+) ions. External Ca (2+) ions are important to voltage-gated K (+) channel function in human atrial myocytes and removal of external Ca (2+) ions affects I (to1) and 4-AP-sensitive I (so) in distinct ways. |
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