Role of beta1- and beta2-adrenergic receptors in regulation of Cl- and Ca2+ channels in guinea pig ventricular myocytes.
The role of beta1- and beta2-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 beta2-receptor antagonist ICI-118,551 (ICI), but it was blocked by the beta1-receptor antagonist atenolol. The inability of beta2-receptor stimulation to activate the Cl- current was confirmed by the lack of response to the selective beta2-receptor agonists salbutamol and zinterol. Responses to beta2-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 beta2- but not beta1-receptor stimulation. PTX treatment increased the sensitivity of the Cl- current to activation by Iso in the presence of ICI, indicating that PTX increases beta1-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 beta1-receptors. These results indicate that PTX treatment increases the sensitivity to beta1-receptor stimulation, without affecting beta2-responsiveness. To verify that the lack of response to beta2-receptor stimulation was not unique to the Cl- current, the effects of beta2-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 beta1-receptors was involved. These results indicate that beta1- but not beta2-adrenergic receptor stimulation plays an important role in modulating the cAMP-regulated Cl- and Ca2+ currents in guinea pig ventricular myocytes.
Hool
L C
LC
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Harvey
R D
RD
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity; D006168:Guinea Pigs; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D018118:Chloride Channels; D002712:Chlorides; D011943:Receptors, Adrenergic, beta; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol