Adenosine-induced changes in atrial action potential: contribution of Ca and K currents.
In this study, we examined the relative contribution of the increase in acetylcholine-regulated potassium current (IK ACh) and decrease in calcium current (ICa) to the adenosine (Ado)-induced shortening of action potential duration (APD). In isolated guinea pig atrial myocytes, membrane potentials and currents were measured by the whole cell patch-clamp technique. ICa and IK ACh were individualized by blocking the K currents with Cs+ and ICa with Cd2+. The effects of Ado on membrane potential and currents were concentration dependent. Ado (10 microM) shortened APD at 0 mV and at 90% of repolarization (APD0,90) to 7 +/- 1 and 26 +/- 6 ms from control values of 23 +/- 3 and 89 +/- 6 ms, respectively. Concomitant with the changes in APD, Ado decreased ICa from -9.2 +/- 1.3 to -6.8 +/- 10 microA/microF (26% decrease) but increased IK ACh from +3.5 +/- 0.5 to +7.8 +/- 0.8 microA/microF (123% increase). When rundown of ICa was taken into account, the maximum decrease in ICa caused by Ado was 12%. The effect of Ado on ICa and IK ACh was not altered by treatment of the cells with either Cs+ or Cd2+. The shortening of ADP0,90 strongly correlated with the increase in IK ACh but minimally with the decrease in ICa. A 22% reduction in ICa caused by lowering extracellular Ca2+ concentration ([Ca2+]o) from 3.6 to 1.8 mM was associated with an 11 and 14% shortening of APD0 and APD90, respectively. In the same myocytes an 18% decrease in ICa by 10 microM Ado reduced APD0 and APD90 by 58 and 61%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Visentin
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Department of Medicine and Pharmacology, College of Medicine, University of Florida, Gainesville 32610.
Wu
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Belardinelli
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D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002586:Cesium / Q000494:pharmacology; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D011188:Potassium / Q000502:physiology*; D011930:Reaction Time
D002104:Cadmium; D002586:Cesium; D000241:Adenosine; D011188:Potassium; D002118:Calcium