title: Differential regulation of low and high voltage-activated calcium channels in neonatal rat myocytes following chronic PKA modulation.
abstract: The biophysical properties of voltage-dependent cardiac calcium channels (VDCC) can be modulated by protein kinases. In this study, we investigate whether long-term treatment with protein kinase A (PKA) modulators alters the VDCC activity in neonatal ventricular myocytes. Using whole-cell patch-clamp recordings, we found an increase in high-voltage activated (HVA) current density and a corresponding decrease in low-voltage activated (LVA) current density in neonatal rat ventricular myocytes up to 6 days in culture. Long-term exposure to 8Br-cAMP, a PKA stimulator, increased the HVA current density at 7 and 24 hours. In contrast, H89, a PKA inhibitor, caused a biphasic change in the HVA, an initial reduction at 7 hours exposure followed by an increase up to 4 days. In addition, H89 caused a sustained increase in LVA currents from 7 hours to 4 days. These findings suggest that chronic exposure to H89 changes LVA and HVA calcium current activities in cardiac myocytes. PKA is a key target of β-adrenoceptor activiation, thus, our findings suggest long-term repeated use of β-adrenergic drugs may induce unexpected functional alteration of VDCCs.
authors.affiliation: Department of Physiology, University of Toronto, ON, Canada.
authors.forename: Kwokyin
authors.initials: K
authors.lastname: Hui
authors.forename: Michelle
authors.initials: M
authors.lastname: Arnot
authors.forename: Hwa-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Hong-Shuo
authors.initials: HS
authors.lastname: Sun
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Feng
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020536:Enzyme Activators / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009124:Muscle Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D020536:Enzyme Activators; D007546:Isoquinolines; D009124:Muscle Proteins; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D013449:Sulfonamides; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide