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CARDIOVASCULAR ANESTHESIA

Propofol Inhibits Volume-Sensitive Chloride Channels in Human Coronary Artery Smooth Muscle Cells

Takako Masuda, MD^*, Yoshinobu Tomiyama, MD^*, Hiroshi Kitahata, MD^*, Yasuhiro Kuroda, MD, and Shuzo Oshita, MD^*

*Department of Anesthesiology and Division of Intensive Care and Critical Care Medicine, Tokushima University School of Medicine, Tokushima, Japan

Address correspondence and reprint requests to Yoshinobu Tomiyama, MD, Department of Anesthesiology, Tokushima University School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. Address e-mail to totomi{at}clin.med.tokushima-u.ac.jp

Volume-sensitive chloride channels (VSCC) play an important role in regulation of cell volume and electrical activity. Activation of vascular smooth muscle VSCC causes smooth muscle depolarization and contraction. We investigated the effects of propofol on VSCC in cultured human coronary artery smooth muscle cells by using the chloride-sensitive dye 6-methoxy-N-ethylquinolinium (MEQ). To activate VSCC, cells were superfused for 2 min with hypotonic gluconate solutions and then potassium thiocyanate solution. The percentage reduction in MEQ fluorescence during 60 s in the presence of potassium thiocyanate was measured and used as an index of VSCC activity. 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a well characterized chloride channel blocker, and propofol were dissolved in hypotonic gluconate solution to test their effect on VSCC activity. The reduction in fluorescence was inversely related to osmolality, indicating that activation of VSCC is osmolality dependent. Hypotonic gluconate solution (210 mOsm/kg H₂O) reduced fluorescence by 38.9% ± 2.6% of the baseline value. The reduction in fluorescence was dose-dependently inhibited by NPPB. Propofol at 0.3, 1, 3, 10, 30, and 100 µg/mL significantly inhibited the reduction in fluorescence to 23.6% ± 4.8%, 19.7% ± 7.4%, 18.2% ± 3.5%, 17.6% ± 5.0%, 15.8% ± 3.1%, and 10.3% ± 3.9% of the baseline value, respectively. Our results indicate that propofol inhibits VSCC in a dose-dependent manner in human coronary artery smooth muscle cells.

IMPLICATIONS: Propofol inhibits human coronary artery smooth muscle volume-sensitive chloride channels in a dose-dependent manner.