ATP-sensitive K+ channels are altered in hypertrophied ventricular myocytes.
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.
Cameron
J S
JS
Department of Biological Sciences, Wellesley College, Massachusetts 02181.
Kimura
S
S
Jackson-Burns
D A
DA
Smith
D B
DB
Bassett
A L
AL
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
D000631:Aminopyridines; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D002118:Calcium