| Objective Dexmedetomidine has been widely used in clinical anesthesia andintensive care units because of its sedative, analgesic, and anxiolytic effectswhich produce by exciting human extensively distributed alpha2adrenoceptors. Continuous infusion of dexmedetomidine may clinically leadto undesirable cardiovascular system responses such as significanthypotension, bradycardia. However, the exact mechanism of these adversereactions is still not well known. Large-conductance Ca2+-activatedpotassium channels (BKCachannel) distribute broadly on the vascularsmooth muscle cell membrane and its activation play an important role invasodilatation. The finding of the effect of dexmedetomidine on the vascularsmooth muscle cell BKCachannel activity has not been reported. To explorethe possible mechanism of dexmedetomidine-associated hypotension, thisexperiment is designed to the investigate effect of different concentration ofdexmedetomidine on BKCachannel of the rat mesenteric artery smoothmuscle（MASM） by use patch clamp technique of single channel currentrecord. Methods The rat mesenteric artery was removed and dissected freeof surrounding connective tissue and fat under microscopic guidance, singlevascular smooth muscle cells were obtained after acute enzymatic hydrolysis. All patch clamp experiments were performed on single smooth muscle cellsin symmetric high potassium solution （[K+]0:[K+]i=140:140mM）. Ioniccurrents were recorded using single channel inside-out patch clamprecording technique at+40mV holding potential in exposure of differentconcentrations of dexmedetomidine (0,10-9,10-8,10-7,10-6,10-5M), andwith Ca2+(10-7mM) or without Ca2+in bath solution. Single channel currentwas amplified and filtered by patch clamp amplifier（CEZ-2200）, thenimported into the computer. Pclamp10.1software was used to record andanalyze Open Probability（Po）, Amplitude（Amp）, mean open Time（To） andmean close Time（Tc）. Results1.In symmetrical high K+solution, singlechannel currents of BKCachannels on the rat mesenteric artery smoothmuscle cells were recorded in inside-out patches. Single channelconductance was216.38±5.92pS （n=8）. The channels were characterized byobvious voltage-dependent and calcium-dependent.48mM TEA could blockthe activities of BKCachannels almost completely.2. In inside-out patcheswithout Ca2+in bath solution, each concentration of the dexmedetomidinehad no any effect on BKCachannels, i.e. no changes in Po, Amp, To and Tccould be found.3. In inside-out patches with the concentration of Ca2+(10-7mM) in bath solution, Tc of channel was significantly shortened（p<0.01） at10-9M and10-8M dexmedetomidine compared with controlgroup（without dexmedetomidine）, but no change found to Po. With thefurther increase of intracellular dexmedetomidine concentration (10-7,10-6, 10-5M), the Po of BKCachannels increased accordingly in a concentration-dependent manner, except to shortening channel Tc.4. There were nochanges in both To and Amp in all concentration groups of thedexmedetomidine. Conclusion BKCachannels on rat mesenteric arterysmooth muscle cells could be activated directly by dexmedetomidine in aconcentration-dependent manner. The mechanism of dexmedetomidine-associated hypotension may be related to BKCachannel activation of arterysmooth muscle cell. |
PDF Full Text Request