A model of beta-adrenergic effects on calcium and potassium current in bullfrog atrial myocytes.
A model of beta-adrenergic and muscarinic cholinergic effects on the bullfrog atrial myocyte has been developed to simulate the dose-dependent effects of isoprenaline (Iso) on the action potential duration (APD); i.e., low doses of Iso lengthen the APD, whereas high doses shorten the APD. In this model, the reduction in APD is the result of 1) calcium-dependent inactivation of calcium current (ICa) resulting from the enhancement of ICa by Iso and 2) an enhancement of potassium current (IK) due to both an Iso-induced increase in the rate of activation of IK and an increase in peak action potential height. The effect of acetylcholine (ACh) is simulated by a reduction in the Iso-induced increase in ICa and IK through a reduction in relative adenosine 3',5'-cyclic monophosphate concentration ([cAMP]), as well as activation of the ACh-sensitive potassium current. At low [Iso] levels in the presence of a high [ACh], the muscarinic cholinergic effects dominate the beta-adrenergic change. However, for a large [Iso] and a small [ACh], this pattern of changes in transmembrane currents is different; in this case the model predicts that ACh can actually increase APD.
Shumaker
J M
JM
Department of Electrical and Computer Engineering, Rice University, Houston, Texas 7725-1892.
Clark
J W
JW
Giles
W R
WR
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials; D000818:Animals; D016275:Atrial Function; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004553:Electric Conductivity; D006321:Heart / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism*; D011892:Rana catesbeiana; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D000242:Cyclic AMP; D007545:Isoproterenol; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium