title: Overexpression of phospholamban alters inactivation kinetics of L-type Ca2+ channel currents in mouse atrial myocytes.
abstract: In mammalian ventricular myocytes, inactivation of L-type Ca2+ channels (CaCh) is controlled by voltage- and Ca2+-dependent mechanisms. The Ca2+-dependent component is regulated by the Ca2+ released from the sarcoplasmic reticulum (SR). However, little is known about the inactivation properties of CaCh in atrial myocytes, which lack spatial coupling between CaCh and SR Ca2+ release channels. The cardiac SR Ca2+ load is determined by the activity of SR Ca2+-ATPase, which is inversely regulated by the levels of phospholamban (PLB). To investigate the role of SR Ca2+ in atrial myocytes, Ca2+ currents (I Ca) were recorded in mouse atrial myocytes recorded from wild-type (WT) mice and the characteristics were compared to those obtained from atrial myocytes from the transgenic mice overexpressing PLB (PLB-OEX). ICa from WT exhibited fast and slow components of inactivation and the rate of inactivation was slowed when SR Ca2+ was depleted by caffeine, suggesting that the inactivation of atrial ICa is modulated by SR Ca2+ load. The current density and voltage-dependence of ICa were similar between the two groups. However, the fast component of inactivation was significantly reduced in PLB-OEX. When Ca2+ was replaced by Ba2+ or in the presence of caffeine, inactivation was slowed and the decay of the current was not significantly different between WT and PLB-OEX. These results suggest that the inactivation of ICa in mouse atrial myocytes involves Ca2+-dependent and voltage-dependent components. The decrease in the faster component of inactivation in PLB-OEX is consistent with the idea that CaCh and SR Ca2+ release channels are functionally coupled and Ca2+ released from the SR contributes the Ca2+-dependent inactivation component.
authors.affiliation: Departments of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267, USA.
authors.forename: H
authors.initials: H
authors.lastname: Masaki
authors.forename: H
authors.initials: H
authors.lastname: Sako
authors.forename: V J
authors.initials: VJ
authors.lastname: Kadambi
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: E G
authors.initials: EG
authors.lastname: Kranias
authors.forename: A
authors.initials: A
authors.lastname: Yatani
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D006325:Heart Atria / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D000099211:Phospholamban