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(Circulation. 2002;106:3111.)
© 2002 American Heart Association, Inc.

Basic Science Reports

Nonselective Cation Currents Regulate Membrane Potential of Rabbit Coronary Arterial Cell

Modulation by Lysophosphatidylcholine

Kuniko Terasawa, MD; Toshiaki Nakajima, MD; Haruko Iida, MD; Kuniaki Iwasawa, MD; Hitoshi Oonuma, MD; Taisuke Jo, MD; Toshihiro Morita, MD; Fumitaka Nakamura, MD; Yoshiharu Fujimori, MD; Teruhiko Toyo-oka, MD; Ryozo Nagai, MD

From the Department of Cardiovascular Medicine (K.T., T.N., H.I., K.I., H.O., T.J., T.M., F.N., T.T., R.N.), University of Tokyo, Tokyo, Japan; and the Department of Cardiology (K.T., Y.F.), Narita Red Cross Hospital, Chiba, Japan.

Correspondence to Dr T. Nakajima, Department of Cardiovascular Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113-8655. E-mail masamasa{at}pb4.so-net.ne.jp

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 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.

Key Words: muscle, smooth • cells • ischemia • ion channels

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