APPS November 2002 Meeting Abstract 1122

Yue-kun Ju, David G. Allen, Department of Physiology and the Institute for Biomedical Research, University of Sydney, NSW 2006.

Dysfunction of the sinoatrial node is well recognised in humans, particularly in ischaemic heart disease and the elderly, and can cause a variety of arrhythmias¹. Although it is well established that ischaemia or metabolic inhibition changes Ca²⁺ handling in the ventricular myocytes, there are no equivalent studies in pacemaker cells.

In present study, on isolated single toad pacemaker cells, we found that the firing rate slowed and the rhythm became irregular within 3-5 min of application of CN^-. These changes were associated with reduced amplitude of the spontaneous Ca²⁺ transients. In 9 cells, Ca²⁺ transients were reduced from 338 ą 30 to 189 ą 37 nM (p< 0.005).

It has been proposed that Ca²⁺ release from SR activates the Na⁺/Ca²⁺ exchanger causing an inward, pacemaker current^2-4. Because the magnitude of the Na⁺/Ca²⁺ exchange current is dependent on the amplitude of the Ca²⁺ transient, modulation of the Ca²⁺ transient influences the heart rate. To investigate whether or not the Na⁺/Ca²⁺ exchanger current was affected by CN^-, we studied Na⁺/Ca²⁺ exchanger tail current by using the nystatin perforated-patch clamp technique. We found that in the presence of CN^-, the amplitude of tail currents was significantly reduced to 63 ą 9 % of the control (p< 0.03, n = 5). Our results suggested that CN^- influences of pacemaker activities through partly inhibition of Na⁺ /Ca²⁺ exchanger currents.

(1) Alboni P, Baggioni GF, Scarfo S, Cappato R, Percoco GF, Paparella N et al. American Journal of Cardiology. 1991;67:1180-1184.