Suppression of β-adrenergic responsiveness of L-type Ca2+ current by IL-1β in rat ventricular myocytes

Abstract

The possible mechanism by which interleukin-1β (IL-1β) affects β-adrenergic responsiveness of L-type Ca2+ current ( I Ca,L) was examined in adult rat ventricular myocytes by use of whole cell patch-clamp techniques. In the presence of isoproterenol (Iso), exposure for 3 min to IL-1β suppressed the Iso-activated I Ca,L. In the presence of IL-1β, the response of I Ca,L to Iso was decreased, and the EC50 for Iso stimulation was increased. However, IL-1β had no effect on [3H]CGP-12177 binding, displacement of [3H]CGP-12177 binding by Iso, or on basal and Iso-enhanced cAMP content. When I Ca,L was activated by extracellular application of forskolin or 8-(4-chlorophenylthio)-cAMP, a membrane-permeable cAMP analog, or by intracellular dialysis with cAMP, IL-1β had little effect on I Ca,L. In contrast, in the presence of cAMP, IL-1β still suppressed the Iso-enhanced I Ca,L. These results show that the IL-1β-induced decrease in β-adrenergic responsiveness of I Ca,L does not result from inhibition of β-adrenoceptor binding, adenylyl cyclase activity, or cAMP-mediated pathways, suggesting a cAMP-independent mechanism.