Characterization of the ATP-inhibited K+ current in canine coronary smooth muscle cells

Pflugers Arch. 1994 May;427(1-2):110-20. doi: 10.1007/BF00585949.

Abstract

Intracellular adenosine triphosphate (ATP)-inhibited K+ currents (IK, ATP) in canine coronary artery smooth muscle cells were characterized in the whole-cell configuration using the suction pipette method. Cells dialysed internally with solutions containing 5 mM ATP (ATPi) showed little detectable whole-cell current at potentials more negative than -30 mV. However, cells dialysed with ATPi-free solutions developed a time- and voltage-independent current which reached a maximum of 132 +/- 25 pA at -40 mV about 10 min following patch rupture. After "run-up", the current showed little "run-down". Concentration-dependent inhibition by ATPi yielded an inhibition constant (Ki) of 350 microM and a Hill coefficient of 2.3. In ATPi-free solutions, the large current at -40 mV was reduced by glibenclamide with a Ki of 20 nM and a Hill coefficient of 0.95. Conversely, in 1 mM ATPi solutions, the small current at -40 mV was increased by P-1075 from 8 +/- 2 pA to 143 +/- 33 pA, with a dissociation constant (Kd) of 0.16 microM and a Hill coefficient of 1.7. The effect of P-1075 was antagonized by glibenclamide. Maximal current density elicited by either ATPi depletion or external application of the channel opener P-1075 was similar with slope conductances of 81 +/- 10 pS/pF and 76 +/- 13 pS/pF respectively in the potential range of -90 to -40 mV. External Ca2+ had no effect on this current. Finally, in 1 mM ATPi, 20 and 50 microM adenosine increased the current slope conductance by 36 +/- 15% and 73 +/- 10% respectively between -90 to -40 mV. The IK, ATP, although very small in these cells, was extremely effective in causing membrane potential hyperpolarization.

MeSH terms

  • Adenosine / pharmacology
  • Adenosine Triphosphate / pharmacology*
  • Animals
  • Coronary Vessels / cytology
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiology*
  • Dogs
  • Dose-Response Relationship, Drug
  • Electric Conductivity
  • Glyburide / pharmacology
  • Guanidines / pharmacology
  • Membrane Potentials
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Osmolar Concentration
  • Potassium / antagonists & inhibitors*
  • Potassium / physiology*
  • Potassium Channels / drug effects
  • Pyridines / pharmacology
  • Rest

Substances

  • Guanidines
  • Potassium Channels
  • Pyridines
  • N-cyano-N'-(1,1-dimethylpropyl)-N''-(3-pyridinyl)guanidine
  • Adenosine Triphosphate
  • Adenosine
  • Potassium
  • Glyburide