Role of beta(1)- and beta(2)-adrenergic receptors in regulation of Cl- and Ca2+ channels in guinea pig ventricular myocytes

The role of beta(1)- and beta(2)-adrenergic receptor stimulation in modulating adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- and Ca2+ currents was investigated with use of guinea pig ventricular myocytes. Activation of the Cl- current by the nonselective beta-receptor agonist isoproterenol (Iso) was not affected by the beta-receptor antagonist 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 pertussis toxin (PTX)-treated myocytes because PTX increases the sensitivity of responses to Iso, and PTX has been reported to increase the responsiveness to beta(2)- but not beta(1)-receptor stimulation. PTX treatment increased the sensitivity of the Cl- current to activation by Iso in the presence of ICI, indicating that PTX increases beta(1)-receptor responsiveness. PTX treatment also resulted in the ability of salbutamol to activate the Cl- current. However, the response to salbutamol was blocked by atenolol but not by appropriate concentrations of ICI, suggesting that salbutamol was activating beta(1)-receptors. These results indicate that PTX treatment increases the sensitivity to beta(1)-receptor stimulation, without affecting beta(2)-responsiveness. To verify that the lack of response to beta(2)-receptor stimulation was not 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 only affected by high concentrations of zinterol or salbutamol, and such responses were blocked by atenolol, but not by ICI, suggesting that activation of beta(1)-receptors was involved. These results indicate that beta(1)- but not beta(2)-adrenergic receptor stimulation plays an important role in modulating the cAMP-regulated Cl- and Ca2+ currents in guinea pig ventricular myocytes.