title: ATP-sensitive K+ channels are altered in hypertrophied ventricular myocytes.
abstract: Unitary K+ currents in single cells isolated from normal and hypertrophied feline left ventricles were studied with regard to ATP sensitivity using patch-clamp single-channel recording. Data were obtained from excised inside-out membrane patches with symmetrical transmembrane K+ concentration [K+] (140 mM) at 22 +/- 1 degree C and in the absence of divalent cations. In the absence of ATP at the intracellular membrane surface, K+ channel activity was observed during depolarizing and hyperpolarizing pulses ranging from 10 to 120 mV from the K+ equilibrium potential. The current voltage (I-V) curve displayed some inward rectification, with slope conductances becoming nonlinear at strong depolarizations. Rectification was particularly pronounced in cells from hypertrophied left ventricles relative to normal. Single-channel conductance determined from the linear portion of the I-V curve was 77 pS in both groups. The channels were blocked by intracellular Ca2+ (1 mM), extracellular tetraethylammonium (TEA; less than or equal to 2 mM) or 4-aminopyridine (0.5 mM); 2 mM ATP produced a total but reversible inhibition. The effect of ATP was to reduce channel openings; conductance was unaffected. The ATP concentration [( ATP]) that induced half-maximal inhibition of channel activity was 75 microM in normal myocytes but was 250 microM in cells from hypertrophied hearts. Rapid channel activation at diminished [ATP] may provide a protective function by maintaining resting potential or promoting vasodilation in hypertrophied myocardium.
authors.affiliation: Department of Biological Sciences, Wellesley College, Massachusetts 02181.
authors.forename: J S
authors.initials: JS
authors.lastname: Cameron
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: D A
authors.initials: DA
authors.lastname: Jackson-Burns
authors.forename: D B
authors.initials: DB
authors.lastname: Smith
authors.forename: A L
authors.initials: AL
authors.lastname: Bassett
mesh_terms: D015761:4-Aminopyridine; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D006332:Cardiomegaly / Q000503:physiopathology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D006352:Heart Ventricles / Q000503:physiopathology; D008564:Membrane Potentials; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D000631:Aminopyridines; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D002118:Calcium