Published online before print August 28, 2003, doi: 10.1161/01.RES.0000093204.25499.83
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Submitted on March 13, 2003
Revised on August 15, 2003
Accepted on August 19, 2003
Mechanosensitive Cation Channels in Arterial Smooth Muscle Cells Are Activated by Diacylglycerol and Inhibited by Phospholipase C Inhibitor
Kyoung Sun Park ;
From the Department of Physiology (K.S.P., Y.K., Y.E.E., W.-K.H.) and National Research Laboratory for Cellular Signalling (K.S.P., Y.E.E.), Seoul National University College of Medicine, Seoul, Korea, and the Department of Physiology (Y.-H.L.), Yonsei University College of Medicine, Seoul, Korea. Y.M. Kim is now at the Department of Physiology, College of Medicine, Chungbuk National University, Cheongju, Korea.
* To whom correspondence should be addressed. E-mail: wonkyung{at}snu.ac.kr.
Mechanosensitive cation channels may be involved in the development of the myogenic tone of arteries. The molecular identity of these channels is not clear, but transient receptor potential channels (TRPCs) are good candidates. In the present study, we searched for mechanosensitive channels at the single-channel level in arterial smooth muscle cells using the patch-clamp technique and investigated the channel properties in the light of properties of TRPCs. With 140 mmol/L CsCl in the pipette solution, application of negative pressures to the back of the pipette induced the activation of channels the open probability of which increased with the amount of negative pressure. The current-voltage relationship was linear in symmetrical ionic conditions, and the single-channel conductances for Cs+, K+, and Na+ were 30, 36, and 27 pS, respectively. When NMDG+ was substituted for Cs+ in the pipette solution, inward currents were abolished, whereas outward currents remained active, indicating that the channels were nonselective to cations. The channel activity was blocked by intracellular Gd3+ and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and increased by diacylglycerol and by cyclopiazonic acid. Phospholipase C inhibitor (U73122) inhibited not only channel activity but also the development of myogenic tone induced by stretching of the basilar arteries. These results suggest that the ion channel responsible for the development of myogenic tone is the 30-pS mechanosensitive cation channel that exhibits properties similar to those of TRPCs.
Key words: mechanosensitive cation channels • transient receptor potential channels • myogenic tone • phospholipase C
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