Cellular basis for the negative dromotropic effect of adenosine on rabbit single atrioventricular nodal cells.
The effects of adenosine on action potentials, rate-dependent activation failure (the cellular basis for second-degree atrioventricular [AV] block), and the recovery of excitability in rabbit isolated single AV nodal cells were studied using the whole-cell patch-clamp technique. Adenosine (1 micromol/L) shortened the duration, depressed the amplitude, and reduced the rate of rise of the AV nodal cell action potential. Adenosine (10 micromol/L) caused a significant hyperpolarization (7 +/- 1 mV) of AV nodal cells. Adenosine increased the occurrence and the rate dependence of activation failure (Wenckebach periodicity) of AV nodal cells: this effect was concentration dependent and mediated by A1 adenosine receptors. The rate-dependent activation failure caused by adenosine was associated with a prolongation of the effective refractory period by 18 +/- 2 ms (P < .05), an increase in the duration of activation delay, and an elevation (from 0.22 +/- 0.04 to 0.30 +/- 0.03 nA, P < .05) of the threshold current amplitude required to activate AV nodal cells. The results suggest that the slowed recovery of excitability of AV nodal cells caused by adenosine forms the cellular basis for adenosine-induced second-degree AV block. Adenosine decreased ICa,L and activated IK,ADO of AV nodal cells. These actions of adenosine on ion currents may contribute to the effect of this nucleoside to depress excitability of AV nodal cells. The enhancement by adenosine of rate-dependent activation failure of AV nodal cells implies that the negative dromotropic effect of adenosine should be more pronounced during an episode of supraventricular tachycardia than during normal rhythm.
Wang
D
D
Department of Pharmacology, University of Florida, Gainesville 32610, USA.
Shryock
J C
JC
Belardinelli
L
L
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function / Q000187:drug effects; D001283:Atrioventricular Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002469:Cell Separation; D006339:Heart Rate / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D009431:Neural Conduction / Q000187:drug effects*; D011817:Rabbits; D011930:Reaction Time / Q000187:drug effects; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
D000241:Adenosine; D002118:Calcium