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dc.contributor.authorBracken, N.*
dc.contributor.authorEl-Kadri, M.*
dc.contributor.authorHart, G.*
dc.contributor.authorHussain, Munir*
dc.date.accessioned2009-09-15T08:40:27Z
dc.date.available2009-09-15T08:40:27Z
dc.date.issued2006
dc.identifier.citationBracken, N., El-Kadri, M., Hart, G. and Hussain, M. (2006). The role of constitutive pka-mediated phosphorylation in the regulation of basal ICa in isolated rat cardiac myocytes. British Journal of Pharmacology. Vol. 148, No. 8, pp. 1108-1115.en
dc.identifier.urihttp://hdl.handle.net/10454/3452
dc.descriptionNoen
dc.description.abstract1 Pharmacological inhibitors of protein kinase A (PKA) and protein phosphatases 1/2A were used to determine whether basal L-type Ca2+ current (ICa) observed in the absence of exogenous ß-adrenergic receptor stimulation is sustained by PKA-mediated phosphorylation. Amphotericin B was used to record whole-cell ICa in the perforated patch-clamp configuration. 2 Calyculin A and isoprenaline (both 1 ¿mol l¿1) increased basal ICa (P<0.05), whereas H-89 inhibited ICa in a concentration-dependent manner with an IC50 ~5 ¿mol l¿1. H-89 also inhibited the response to 1.0 ¿mol l¿1 isoprenaline, although relatively high concentrations (30 ¿mol l¿1) were required to achieve complete suppression of the response. 3 Double-pulse protocols were used to study the effects of 10 ¿mol l¿1 H-89 on time-dependent recovery of ICa from voltage-dependent inactivation as well as the steady-state gating of ICa. T0.5 (time for ICa to recover to 50% of the preinactivation amplitude) increased in the presence of H-89 (P<0.05) but was unaffected by calyculin A or isoprenaline. 4 Steady-state activation/inactivation properties of ICa were unaffected by 10 ¿mol l¿1 H-89 or 1 ¿mol l¿1 calyculin A, whereas isoprenaline caused a leftward shift in both curves so that V0.5 for activation and inactivation became more negative. 5 Data show that basal ICa is regulated by cAMP-PKA-mediated phosphorylation in the absence of externally applied ß-receptor agonists and that relatively high concentrations of H-89 are required to fully suppress the response to ß-adrenergic receptor stimulation, thereby limiting the value of H-89 as a useful tool in dissecting signalling pathways in intact myocytes.en
dc.language.isoenen
dc.subjectCardiac myocytesen
dc.subjectCalcium currenten
dc.subjectProtein kinase Aen
dc.subjectH-89en
dc.subjectCalyculin Aen
dc.titleThe role of constitutive pka-mediated phosphorylation in the regulation of basal ICa in isolated rat cardiac myocytes.en
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen
dc.identifier.doihttps://doi.org/10.1038/sj.bjp.0706809


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