ISSN:
1432-2013
Keywords:
Key words Phenylephrine
;
Ca2+ transient
;
L-type Ca2+ current
;
Contractile amplitude
;
PKC
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The effects of α1-adrenoceptor stimulation on intracellular Ca2+ transients, contractility and L-type Ca2+ current (I Ca,L) were studied in single cells isolated from ventricles of guinea-pig hearts. The aim of our study was to elucidate the mechanisms of the positive inotropic effect of α1-adrenergic stimulation by focussing on the role of protein kinase C (PKC). Phenylephrine, an α1-adrenergic agonist, at concentrations of 50–100 µM elicited a biphasic inotropic response: a transient negative inotropic response (22.9±6.0% of control) followed by a sustained positive inotropic response (61.0±8.4%, mean±SE, n=12). The Ca2+ transient decreased by 10.2±3.9% during the negative inotropic phase, while it increased by 67.7±10% (n=12) during the positive inotropic phase. These effects were inhibited by prazosin (1 µM), a α1-adrenergic antagonist. Phenylephrine increased the I Ca,L by 60.8±21% (n=5) during the positive inotropic phase. To determine whether activation of PKC is responsible for the increases in Ca2+ transients, contractile amplitude and I Ca,L during α1-adrenoceptor stimulation, we tested the effects of 4β-phorbol 12-myristate 13-acetate (PMA), a PKC activator, and of bisindolylmaleimide I (GF109203X) and staurosporine, both of which are PKC inhibitors. PMA mimicked phenylephrine’s effects on Ca2+ transients, contractile amplitude and I Ca,L. PMA (100 nM) increased the Ca2+ transient, contractile amplitude and I Ca,L by 131±17%, 137±25% (n=8), and 81.1±26% (n=5), respectively. Prior exposure to GF109203X (1 µM) or staurosporine (10 nM) prevented the phenylephrine-induced increases in Ca2+ transients, contractile amplitude and I Ca,L. Our study suggests that during α1-adrenoceptor stimulation increase in I Ca,L via PKC causes an increase in Ca2+ transients and thereby in the contractile force of the ventricular myocytes.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004240050787
Permalink
