Does the small conductance Ca-activated K current I flow under physiological conditions in rabbit and human atrial isolated cardiomyocytes?

BACKGROUND

The small conductance Ca-activated K current (I) is a potential therapeutic target for treating atrial fibrillation.

AIM

To clarify, in rabbit and human atrial cardiomyocytes, the intracellular [Ca]-sensitivity of I, and its contribution to action potential (AP) repolarisation, under physiological conditions.

METHODS

Whole-cell-patch clamp, fluorescence microscopy: to record ion currents, APs and [Ca]; 35-37°C.

RESULTS

In rabbit atrial myocytes, 0.5 mM Ba (positive control) significantly decreased whole-cell current, from -12.8 to -4.9 pA/pF (P < 0.05, n = 17 cells, 8 rabbits). By contrast, the I blocker apamin (100 nM) had no effect on whole-cell current, at any set [Ca] (∼100-450 nM). The I blocker ICAGEN (1 μM: ≥2 x IC) also had no effect on current over this [Ca] range. In human atrial myocytes, neither 1 μM ICAGEN (at [Ca] ∼ 100-450 nM), nor 100 nM apamin ([Ca] ∼ 250 nM) affected whole-cell current (5-10 cells, 3-5 patients/group). APs were significantly prolonged (at APD and APD) by 2 mM 4-aminopyridine (positive control) in rabbit atrial myocytes, but 1 μM ICAGEN had no effect on APDs, versus either pre-ICAGEN or time-matched controls. High concentration (10 μM) ICAGEN (potentially I-non-selective) moderately increased APD and APD, by 5 and 26 ms, respectively. In human atrial myocytes, 1 μM ICAGEN had no effect on APD, whether stimulated at 1, 2 or 3 Hz (6-9 cells, 2-4 patients/rate).

CONCLUSION

I does not flow in human or rabbit atrial cardiomyocytes with [Ca] set within the global average diastolic-systolic range, nor during APs stimulated at physiological or supra-physiological (≤3 Hz) rates.