title: 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: 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.
  
  
  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.
authors.affiliation: Departments of Anesthesiology, Medicine, and Pharmacology, University of Florida, Gainesville, FL, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Martynyuk
authors.forename: T E
authors.initials: TE
authors.lastname: Morey
authors.forename: L
authors.initials: L
authors.lastname: Belardinelli
authors.forename: D M
authors.initials: DM
authors.lastname: Dennis
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000502:physiology*; D017609:Barium Compounds / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D006168:Guinea Pigs; D006947:Hyperkalemia / Q000503:physiopathology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials; D009206:Myocardium / Q000166:cytology*; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D015221:Potassium Channels; C024986:barium chloride; D000241:Adenosine; D007545:Isoproterenol; D011188:Potassium