Vagal control of heart rate is modulated by extracellular potassium

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-a trial node, in particular the acetylcholine-activated potassium current (I- K,I-ACh), the hyperpolarization-activated current (I-f) and the L-type calc ium current (I-Ca,I-L), we investigated whether mimicking [K+](0) concentra tions seen during and immediately after exercise could directly modulate th e HR response to vagal nerve stimulation (VNS) in the isolated guinea-pig a tria preparation pre-stimulated with nondrenaline (NA, I mu M). Lowering [K +](0) from 4 to 3 mM significantly enhanced the HR response to VNS (5 Hz, 5 V, 30 s, Delta HR 84.5 +/- 14.1 bpm and 119.3 +/- 18.2 bpm, respectively). Increasing [K+](0) to 8 or 10 mh I significantly decreased the drop in HR with VNS in comparison to the response to 3 mM K+ Tyrode (Delta HR 56.4 +/- 9.1 bpm and 52.1 +/- 8.7 bpm, respectively). These results could be simula ted using the OXSOFT heart sino-atrial node computer model by activating I- K,I-ACh during changes in [K+](0). However, changing [K+](0) in the model h ad no significant effect on the decrease in beating frequency brought about by decreasing If or Ic,, 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 in creased 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 effect s of changes in [K+](0) on the current-voltage relationship for I-K,I-ACh. (C) 1999 Elsevier Science B.V. All rights reserved.