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

Article

关键词: MUSCARINIC K+ CHANNELS;    ATRIOVENTRICULAR NODE;    MYOCARDIAL ISCHEMIA;    IONIC BASIS;    CELLS;    ACETYLCHOLINE;    ACTIVATION;    OCCLUSION;    PACEMAKER;    EXERCISE;   

DOI  :  10.1161/01.CIR.99.2.312

来源: SCIE

【 摘 要 】

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 (I-K1). However, we propose that in the presence of adenosine, elevated [K+](o) should increase the adenosine-activated inward rectifier potassium current (I-K,I-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 (V-m), I-K,I-ADO, and membrane resistance (R-m) in rabbit isolated AV nodalmyocytes 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, R-m, or V-m in AV nodal myocytes. However, high [K+](o) in the presence of adenosine (3 mu mol/L) markedly increased I-m (-0.249+/-0.038 to -0.571+/-0.111 nA, P<0.05) at -100 mV and reduced R-m (151+/-21 to 77+/-8 M Omega, P<0.02). Adenosine still hyperpolarized V-m 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 mu mol/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 mu mol/L). Conclusions-By increasing I-K,I-ADO and decreasing R-m of AV nodal myocytes, elevated [K+](o), augments the depressant effect of adenosine on AV nodal conduction.

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