title: Plasmalemmal KATP channels shape triggered calcium transients in metabolically impaired rat atrial myocytes.
abstract: The relative role of plasmalemmal and mitochondrial ATP-sensitive K(+) (K(ATP)) channels in calcium homeostasis of the atrium is little understood. Electrically triggered (1 Hz) cytoplasmic calcium transients were measured by 340-to-380-nm wavelength fura 2 emission ratios in cultured rat atrial myocytes. CCCP, a mitochondrial protonophore (100-400 nmol/l), dose dependently reduced the transient amplitude by up to 85%, caused a slow rise in baseline calcium, and reduced the recovery time constant of the transient from 143 to 91 ms (P < 0.05). However, neither 5-hydroxydecanoate, a mitochondrial K(ATP) channel blocker, nor diazoxide (500 micromol/l) affected the amplitude, baseline, or time constant in CCCP-treated cells. HMR-1098 (30 micromol/l), a plasmalemmal K(ATP) channel blocker, and glibenclamide (1 micromol/l) increased the amplitude in CCCP-treated myocytes by 69-82%, sharply elevated the calcium baseline, and prolonged the recovery time constant to 181-193 ms (P < 0.01). Thus opening of plasmalemmal but not mitochondrial K(ATP) channels reduces the calcium overload in metabolically compromised but otherwise intact atrial myocytes. Mitochondrial K(ATP) channels probably operate through a different mechanism to afford ischemic protection.
authors.affiliation: Department of Physiology, Centre Médical Universitaire, 1211 Geneva 4, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Baumann
authors.forename: Serge
authors.initials: S
authors.lastname: Poitry
authors.forename: Angela
authors.initials: A
authors.lastname: Roatti
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Baertschi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D020517:Atrial Appendage / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D005905:Glyburide / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000889:Anti-Arrhythmia Agents; D005456:Fluorescent Dyes; D007476:Ionophores; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium