Hyperkalemia Enhances the Effect of Adenosine on I K,ADO in Rabbit Isolated AV Nodal Myocytes and on AV Nodal Conduction in Guinea Pig Isolated Heart

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: By increasing IK,ADO and decreasing Rm of AV nodal myocytes, elevated [K+]o, augments the depressant effect of adenosine on AV nodal conduction.