ROLE OF BETA(1)-ADRENERGIC AND BETA(2)-ADRENERGIC RECEPTORS IN REGULATION OF CL- AND CA2-PIG VENTRICULAR MYOCYTES( CHANNELS IN GUINEA)

The role of beta(1)- and beta(2)-adrenergic receptor stimulation in mo dulating adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- and Ca2+ currents was investigated with use of guinea pig ventricular myo cytes. Activation of the Cl- current by the nonselective beta-receptor agonist isoproterenol (Iso) was not affected by the beta-receptor ant agonist ICI-118,551 (ICI), but it was blocked by the beta(1)-receptor antagonist atenolol. The inability of beta(2)-receptor stimulation to activate the Cl- current was confirmed by the lack of response to the selective beta(2)-receptor agonists salbutamol and zinterol. Responses to beta(2)-adrenergic receptor stimulation were also looked for in pe rtussis toxin (PTX)-treated myocytes because PTX increases the sensiti vity of responses to Iso, and PTX has been reported to increase the re sponsiveness to beta(2)- but not beta(1)-receptor stimulation. PTX tre atment increased the sensitivity of the Cl- current to activation by I so in the presence of ICI, indicating that PTX increases beta(1)-recep tor responsiveness. PTX treatment also resulted in the ability of salb utamol to activate the Cl- current. However, the response to salbutamo l was blocked by atenolol but not by appropriate concentrations of ICI , suggesting that salbutamol was activating beta(1)-receptors. These r esults indicate that PTX treatment increases the sensitivity to beta(1 )-receptor stimulation, without affecting beta(2)-responsiveness. To v erify that the lack of response to beta(2)-receptor stimulation was no t unique to the Cl- current, the effects of beta(2)-receptor agonists on the L-type Ca2+ current were also examined. The Ca2+ current was on ly affected by high concentrations of zinterol or salbutamol, and such responses were blocked by atenolol, but not by ICI, suggesting that a ctivation of beta(1)-receptors was involved. These results indicate th at beta(1)- but not beta(2)-adrenergic receptor stimulation plays an i mportant role in modulating the cAMP-regulated Cl- and Ca2+ currents i n guinea pig ventricular myocytes.