Modulation of ICa-L by alpha(1)-adrenergic stimulation in rat ventricular myocytes

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dc.contributor.authorZhang, ST
dc.contributor.authorLin, JJ
dc.contributor.authorHirano, YJ
dc.contributor.authorHiraoka, M
dc.date.accessioned2007-10-30T14:59:23Z
dc.date.available2007-10-30T14:59:23Z
dc.date.issued2005-11-30
dc.description.abstractWe found when L-type calcium current (ICa-L) was recorded with the perforated patch-clamp method in rat ventricular myocytes that bath application of phenylephrine (with propranolol) evoked a biphasic response characterized by an initial transient suppression followed by a sustained potentiation. The transient suppression occurred 30-60 s after phenylephrine perfusion and reached peak inhibition at approximately 2 min. The biphasic modulation of ICa-L was also elicited by methoxamine, and the effects of phenylephrine were blocked by prazosin, indicating that the responses were mediated through alpha(1)-adrenoceptors. Pretreatment of cells with H7 (100 mu mol/L), a broad-spectrum protein kinase inhibitor that inhibits both protein kinase C and A, eliminated potentiation but did not affect transient suppression. The transient suppression occurred concurrently with the acceleration of the fast component of ICa-L inactivation. Depletion of intracellular Ca2+ stores by ryanodine plus caffeine or thapsigargin eliminated the transient suppression. When ICa-L was recorded with whole-cell patch-clamp and with 0.05 mmol/L EGTA in the pipette solution to allow intracellular Ca2+ to fluctuate, phenylephrine evoked a transient suppression as in the perforated patch recordings. Heparin, a specific blocker of IP3 (inositol 1,4,5-trisphosphate) receptors, eliminated the phenylephrine-induced transient suppression of ICa-L when added to the pipette solution. Intensive chelation of intracellular Ca2+ by 5 mmol/L BAPTA (1,2-bis(2aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) in the pipette solution also eliminated the phenylephrine-induced transient suppression of ICa-L We conclude that transient increase in the concentration of intracellular calcium ([Ca2+](i)) caused by Ca2+ release from intracellular stores underlies the transient suppression of ICa-L, whereas the potentiation of ICa-L is a result of activation of protein kinases.en
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dc.identifier.citation0008-4212; CAN J PHYSIOL PHARMACOL, NOV 2005, vol. 83, no. 11, p.1015 to 1024.en
dc.identifier.urihttp://hdl.handle.net/1993/2961
dc.language.isoengen_US
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dc.rightsopen accessen_US
dc.statusPeer revieweden
dc.subjectCa2(+) mobilizationen
dc.subjectIP3en
dc.subjectCa2+-induced inactivation of Ca2+ currenten
dc.subjectperforated patch-clampen
dc.subjectPROTEIN-KINASE-Cen
dc.subjectCARDIAC PURKINJE-FIBERSen
dc.subjectSMOOTH-MUSCLE CELLSen
dc.subjectCALCIUM-CHANNELSen
dc.subjectALPHA-1-ADRENOCEPTOR STIMULATIONen
dc.subjectSIGNAL-TRANSDUCTIONen
dc.subjectMAMMALIAN HEARTen
dc.subjectANGIOTENSIN-IIen
dc.subjectCA2+ CURRENTen
dc.subjectK+ CURRENTen
dc.titleModulation of ICa-L by alpha(1)-adrenergic stimulation in rat ventricular myocytesen
dc.typejournal articleen_US
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