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1- and
2-adrenergic receptors in
regulation of Cl
and
Ca2+ channels in guinea pig
ventricular myocytes
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106
The role of
1- and
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 -receptor agonist isoproterenol (Iso) was not affected
by the 2-receptor antagonist
ICI-118,551 (ICI), but it was blocked by the
1-receptor antagonist atenolol. The inability of 2-receptor
stimulation to activate the
Cl current was confirmed by
the lack of response to the selective 2-receptor agonists salbutamol
and zinterol. Responses to
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
2- but not
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
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
1-receptors. These results
indicate that PTX treatment increases the sensitivity to
1-receptor stimulation, without
affecting 2-responsiveness. To
verify that the lack of response to
2-receptor stimulation was not
unique to the Cl current,
the effects of 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
1-receptors was involved. These
results indicate that 1- but
not 2-adrenergic receptor stimulation plays an important role in modulating the cAMP-regulated Cl and
Ca2+ currents in guinea pig
ventricular myocytes.
pertussis toxin-sensitive G protein; isoproterenol; salbutamol; zinterol; ICI-118,551
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