Small-conductance calcium-activated potassium channels (SK channels) have been suggested to mediate abnormal atrial electrophysiology in heart failure and sustained atrial fibrillation [1 , 2]. However, a mechanistic explanation of the function of SK channels in health and disease is lacking. In this study we examined the effects of a putatively specific SK channel blocker on the electrophysiology of atria and ventricle of rabbit hearts. Experiments were performed in isolated atrial cardiomyocytes and intact atria and ventricle of isolated rabbit hearts using fluorescence based methods. Isolated Langendorff perfused hearts were perfused with Di-4-ANEPPS to allow measurements of atrial and ventricular action potentials (APs) optically. Addition of the drug (1µM) to the perfusate caused significant prolongation of atrial AP duration (APD) at 5mins, (APD75 19.52% change +/- 2.4 and APD90 23.90% change +/- 6.63 ,n=4), but no change in ventricular APD (APD75 3.03% change +/- 1.70, APD90 2.30% change +/-0.84, n=4). This effect was confirmed with corresponding, independent, experiments in isolated atrial and ventricular cells. To test the dependence of the effect on intracellular calcium, the effect of the drug in hearts perfused for 20mins in low (0.3mM) extracellular Ca2+ was examined. This manoeuvre which was designed to lower intracellular Ca2+ did not alter the drug-induced prolongation of APD . Similar results were observed in isolated atrial myocytes. This apparent lack of sensitivity of the ICAGEN effect to intracellular Ca2+ is counter to the supposed Ca2+- dependence of SK channels. Further studies are required to understand the mechanism underlying the electrophysiological effects of the drug and the SK channel in rabbit atrial electrophysiology.
Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, C111
Oral Communications: The effect of the small conducatance calcium-activated potassium channel (SK) inhibitor ICAGEN in intact atria and atrial cardiomyocytes
S. Dobi1, A. Campbell1, A. J. Workman1, G. L. Smith1
1. Institute of Cardiovascular and Medical Sciences, Glasgow, United Kingdom.
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The effect of 5 min ICAGEN perfusion in the rabbit atria in physiological calcium concentration and low calcium
Calcium manipulations and their effect in APDs (Action Potential Duration)<\#13>All values reported as the mean (n=4) APD value in % change in comparison to the baseline � SEM (Standard Error of the Mean)
Where applicable, experiments conform with Society ethical requirements.