Hyperkalemia enhances the effect of adenosine on IK,ADO in rabbit isolated AV nodal myocytes and on AV nodal conduction in guinea pig isolated heart.

Abstract

The atrioventricular (AV) node is insensitive to changes in extracellular potassium concentration, [K+]o, because of the absence of the inward rectifier potassium current (IK1). However, we propose that in the presence of adenosine, elevated [K+]o should increase the adenosine-activated inward rectifier potassium current (IK,ADO) in AV nodal myocytes and hence augment the negative dromotropic effect of the nucleoside. The effects of normal (4.8 mmol/L) and high (8.0 mmol/L) [K+]o on adenosine-induced changes in resting membrane potential (Vm), IK,ADO, and membrane resistance (Rm) in rabbit isolated AV nodal myocytes and in AV nodal conduction delay (atrium-to-His bundle, AH, interval) in guinea pig isolated hearts were determined with the use of whole-cell patch-clamp and His bundle electrogram techniques, respectively. High [K+]o alone did not significantly affect membrane current, Rm, or Vm in AV nodal myocytes. However, high [K+]o in the presence of adenosine (3 micromol/L) markedly increased Im (-0. 249+/-0.038 to -0.571+/-0.111 nA, P<0.05) at -100 mV and reduced Rm (151+/-21 to 77+/-8 MOmega, P<0.02). Adenosine still hyperpolarized Vm from -48+/-2 to -65+/-1 mV (P<0.001). High [K+]o alone did not significantly affect the AH interval in isolated hearts. However, high [K+]o markedly lengthened the AH interval prolongation caused by adenosine (4 micromol/L, 7.9+/-0.8 vs 22.1+/-3.0 ms, P<0.001). The potentiating effect of high [K+]o on adenosine-induced delay in AV nodal conduction was abolished by BaCl2 (100 micromol/L). By increasing IK,ADO and decreasing Rm of AV nodal myocytes, elevated [K+]o, augments the depressant effect of adenosine on AV nodal conduction.