Nonselective cation currents regulate membrane potential of rabbit coronary arterial cell: modulation by lysophosphatidylcholine

Circulation. 2002 Dec 10;106(24):3111-9. doi: 10.1161/01.cir.0000039345.00481.1d.

Abstract

Background: The effects of lysophosphatidylcholine (LPC) on electrophysiological activities and intracellular Ca2+ concentration ([Ca2+]i) were investigated in coronary arterial smooth muscle cells (CASMCs).

Methods and results: The patch clamp techniques and Ca2+ measurements were applied to cultured rabbit CASMCs. The membrane potential was -46.0+/-5.0 mV, and LPC depolarized it. Replacement of extracellular Na+ with NMDG+ hyperpolarized the membrane and antagonized the depolarizing effects of LPC. In Na+-, K+-, or Cs+-containing solution, the voltage-independent background current with reversal potential (E(r)) of approximately +0 mV was observed. Removal of Cl- failed to affect it. When extracellular cations were replaced by NMDG+, E(r) was shifted to negative potentials. La3+ and Gd3+ abolished the background current, but nicardipine and verapamil did not inhibit it. In Na+-containing solution, LPC induced a voltage-independent current with E(r) of approximately +0 mV concentration-dependently. Similar current was recorded in K+- and Cs+-containing solution. La3+ and Gd3+ inhibited LPC-induced current, but nicardipine and verapamil did not inhibit it. In cell-attached configurations, single-channel activities with single-channel conductance of approximately 32pS were observed when patch pipettes were filled with LPC. LPC increased [Ca2+]i as the result of Ca2+ influx, and La3+ completely antagonized it.

Conclusions: These results suggest that (1) nonselective cation current (I(NSC)) contributes to form membrane potentials of CASMCs and (2) LPC activates I(NSC), resulting in an increase of [Ca2+]i. Thus, LPC may affect CASMC tone under various pathophysiological conditions such as ischemia.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Cells, Cultured
  • Cesium / pharmacology
  • Coronary Vessels / cytology*
  • Dose-Response Relationship, Drug
  • Electric Stimulation / methods
  • Gadolinium / pharmacology
  • Intracellular Fluid / metabolism
  • Ion Channels / drug effects
  • Ion Channels / metabolism*
  • Lanthanum / pharmacology
  • Lysophosphatidylcholines / metabolism*
  • Lysophosphatidylcholines / pharmacology
  • Male
  • Meglumine / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium Channel Blockers / pharmacology
  • Rabbits
  • Sodium / metabolism

Substances

  • Calcium Channel Blockers
  • Ion Channels
  • Lysophosphatidylcholines
  • Potassium Channel Blockers
  • Cesium
  • Meglumine
  • Lanthanum
  • Sodium
  • Gadolinium
  • Potassium
  • Calcium