Vagal control of heart rate is modulated by extracellular potassium

Abstract

Heart rate (HR) recovery from heavy exercise is associated with a shift in cardiac sympatho-vagal balance and a transient hypokalaemia. Since changes in extracellular potassium ([K +] 0) affect membrane currents in the sino-atrial node, in particular the acetylcholine-activated potassium current ( I K,ACh), the hyperpolarization-activated current ( I f) and the L-type calcium current ( I Ca,L), we investigated whether mimicking [K +] 0 concentrations seen during and immediately after exercise could directly modulate the HR response to vagal nerve stimulation (VNS) in the isolated guinea-pig atria preparation pre-stimulated with noradrenaline (NA, 1 μM). Lowering [K +] 0 from 4 to 3 mM significantly enhanced the HR response to VNS (5 Hz, 5 V, 30 s, ΔHR 84.5±14.1 bpm and 119.3±18.2 bpm, respectively). Increasing [K +] 0 to 8 or 10 mM significantly decreased the drop in HR with VNS in comparison to the response to 3 mM K + Tyrode (ΔHR 56.4±9.1 bpm and 52.1±8.7 bpm, respectively). These results could be simulated using the OXSOFT heart sino-atrial node computer model by activating I K,ACh during changes in [K +] 0. However, changing [K +] 0 in the model had no significant effect on the decrease in beating frequency brought about by decreasing I f or I Ca,L. We conclude that the magnitude of the decrease in HR with VNS is enhanced in low [K +] 0 and reduced in high [K +] 0. The increased efficacy of cardiac vagal activation in low [K +] 0 might therefore facilitate the drop in HR after heavy exercise where there is a transient hypokalaemia. Modelling suggests this result may be explained by the effects of changes in [K +] 0 on the current–voltage relationship for I K,ACh.