Role of β1- and β2-adrenergic receptors in regulation of Cl- and Ca2+ channels in guinea pig ventricular myocytes

Livia C. Hool, Robert D. Harvey

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30 Citations (Scopus)

Abstract

The role of β1- and β2-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 β-receptor agonist isoproterenol (Iso) was not affected by the β2-receptor antagonist ICI- 118,551 (ICI), but it was blocked by the β1-receptor antagonist atenolol. The inability of β2-receptor stimulation to activate the Cl- current was confirmed by the lack of response to the selective β2-receptor agonists salbutamol and zinterol. Responses to β2-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 β2- but not β1-receptor stimulation. PTX treatment increased the sensitivity of the Cl- current to activation by Iso in the presence of ICI, indicating that PTX increases β1-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 β1-receptors. These results indicate that PTX treatment increases the sensitivity to β1-receptor stimulation, without affecting β2-responsiveness. To verify that the lack of response to β2- receptor stimulation was not unique to the Cl-current, the effects of β2- 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 β1-receptors was involved. These results indicate that β1- but not β2-adrenergic receptor stimulation plays an important role in modulating the cAMP-regulated Cl- and Ca2+ currents in guinea pig ventricular myocytes.

Original languageEnglish
Pages (from-to)H1669-H1676
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume273
Issue number4 42-4
DOIs
Publication statusPublished - 1997
Externally publishedYes

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