SWELLING-INDUCED DECREASE IN SPONTANEOUS PACEMAKER ACTIVITY OF RABBITISOLATED SINOATRIAL NODE CELLS

The heart responds to an increase in sino-atrial node wall stress with an augmentation in rate of contraction. It has been suggested that sw elling-activated ion channels may play a key role in that response. Th is paper investigates directly the effects of cell swelling on spontan eous activity of rabbit isolated sino-atrial node pacemaker cells. The main finding is that sino-atrial node cells, studied in current clamp mode using amphotericin-permeabilized patches, decrease their spontan eous pacemaker rate by 24.2 +/- 7.8% (P < 0.01, n = 9) during 75% hypo smotic swelling. This response is opposite to the predicted impact of volume-activation of sarcolemmal ion conductances. Computer modelling (OXSOFT(C) Heart v4.8) suggests that swelling-induced dilution of the cytosol, reduction in intracellular potassium concentration, and decre ase in the delayed rectifier potassium current, I-K, are leading mecha nisms in the response. This is supported by voltage-clamp data that sh ow a swelling-induced positive shift in the reversal potential of I-K by between 5 and 10 mV(n = 7) and a reduction in amplitude of its rapi dly activating component, I-Kr, (n = 6). Thus, spontaneously active si no-atrial node cells reduce pacemaking rate during swelling. This resp onse cannot be explained by the known volume-activated sarcolemmal ion conductances, but appears to be dictated by other mechanisms includin g dilution of the cytosol and reduction in I-K. The results re-enforce the view that cardiac responses to cell volume changes may be quite d ifferent from those to longitudinal stretch.