title: Cardiac sarcoplasmic reticulum chloride channels regulated by protein kinase A.
abstract: In heart cells, several plasma membrane ion channels are targets for phosphorylation. However, it is not known whether sarcoplasmic reticulum (SR) ion channels, which are also essential in the regulation of cardiac function, are regulated by second-messenger systems. Here, we show that a Cl- channel in the cardiac SR membrane is activated by the catalytic subunit of protein kinase A (PKA). Purified cardiac heavy SR vesicles were incorporated into planar lipid bilayers. This channel spontaneously inactivated within a few minutes after the channel was incorporated into the bilayer. Mg-ATP (2-5 mM), but not the nonhydrolyzable ATP analogue 5'-adenylylimidodiphosphate, added to the cis solution prevented this spontaneous channel inactivation. After the inactivation process occurred, the catalytic subunit of PKA (with 0.05 mM Mg-ATP) reactivated this channel. These effects of Mg-ATP and PKA on the Cl- channel were prevented by an inhibitor of PKA. Thus, these results suggest that this SR Cl- channel is a novel target of PKA-dependent phosphorylation in cardiac muscle regulation.
authors.affiliation: Department of Cardiovascular Disease, Tokyo Medical and Dental University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kawano
authors.forename: F
authors.initials: F
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Hiraoka
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D018118:Chloride Channels; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013552:Swine
chemical_list: D018118:Chloride Channels; D008051:Lipid Bilayers; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D011494:Protein Kinases