Contribution of I(K,ADO) to the negative dromotropic effect of adenosine.
OBJECTIVE
Despite the pathophysiological and therapeutic significance of the negative dromotropic effect of adenosine, its underlying ionic mechanism, and specifically the role of the adenosine-activated K(+) current (I(K,ADO)) is not experimentally defined. Therefore, we studied the contribution of I(K,ADO) to the negative dromotropic effect of adenosine.


METHODS
Effects of adenosine on single atrioventricular nodal and left atrial myocytes from rabbits were studied using the whole cell configuration of the patch clamp technique. Complementary experiments were done in rabbit and guinea pig isolated hearts instrumented to measure the atrium-to-His bundle interval.


RESULTS
In contrast to its effect in atrial myocytes, Ba(2+) selectively and completely blocked I(K,ADO) at membrane potentials from -70 to 0 mV in atrioventricular nodal myocytes and abolished the adenosine-induced leftward shift of the reversal membrane potential. Ba(2+) alone did not significantly prolong the A-H interval, but markedly attenuated the A-H interval prolongation caused by adenosine. In guinea pig heart, EC(50) values ( pD(2) +/- SEM) for adenosine-induced atrium-to-His bundle interval prolongation were 3.3 micromol/L (5.48 +/- 0.04) and 13.2 micromol/L (4.88 +/- 0.05, P < 0.001) in the absence and presence of Ba(2+), respectively. Despite species-dependent differences in sensitivities to adenosine (guinea pig > rabbit), the relative contribution of adenosine-activated K(+) current to the atrium-to-His bundle interval prolongation was nearly identical. In guinea pig hearts it ranged from 37.8 % (P = 0.013) to 72.5 % (P < 0.001) at 2 to 6 micromol/L adenosine, respectively.


CONCLUSIONS
I(K,ADO) contributes significantly to the negative dromotropic effect of adenosine, but predominantly at relatively high concentrations of the nucleoside.
Martynyuk
Anatoly E
AE
Department of Anesthesiology, University of Florida, Gainesville, Florida 32610-0254, USA.
Seubert
Christoph N
CN
Zima
Aleksey
A
Morey
Timothy E
TE
Belardinelli
Luiz
L
Lin
Guilan
G
Cucchiara
Roy F
RF
Dennis
Donn M
DM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000166:cytology / Q000378:metabolism*; D001464:Barium / Q000494:pharmacology; D002036:Bundle of His / Q000166:cytology / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D010477:Perfusion; D011188:Potassium / Q000493:pharmacokinetics; D015221:Potassium Channels / Q000378:metabolism*; D011817:Rabbits
D002121:Calcium Channel Blockers; D015221:Potassium Channels; D001464:Barium; D004110:Diltiazem; D000241:Adenosine; D011188:Potassium