Suppression of beta-adrenergic responsiveness of L-type Ca2+ current by IL-1beta in rat ventricular myocytes.
The possible mechanism by which interleukin-1beta (IL-1beta) affects beta-adrenergic responsiveness of L-type Ca2+ current (ICa,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-1beta suppressed the Iso-activated ICa,L. In the presence of IL-1beta, the response of ICa,L to Iso was decreased, and the EC50 for Iso stimulation was increased. However, IL-1beta 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 ICa,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-1beta had little effect on ICa,L. In contrast, in the presence of cAMP, IL-1beta still suppressed the Iso-enhanced ICa,L. These results show that the IL-1beta-induced decrease in beta-adrenergic responsiveness of ICa,L does not result from inhibition of beta-adrenoceptor binding, adenylyl cyclase activity, or cAMP-mediated pathways, suggesting a cAMP-independent mechanism.
Liu
S J
SJ
Department of Biopharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Zhou
W
W
Kennedy
R H
RH
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology; D004553:Electric Conductivity; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism*; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D007375:Interleukin-1; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP