- 作者: Chih-Fen Huang Ming-Jai Su
- 作者服務機構: Department of Pharmacology and School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: (+)-MK801, a noncompetitive NMDA receptor antago-nist, was reported to exhibit anticonvulsive and neuro-protective activities during the postischemic period, In-travenous administration of (+)-MK801 produced tachy-cardia in rats, but bradycardia in pigs. We examined themechanical and electrophysiological effects of (+)-MK801 on rat cardiac tissues. (+)-MK801 dose-depen-dently increased(3-100μM)twitch tension in rat atriaand ventricular strips. The spontaneous beating rate inrat right atria, however, was dose-dependently de-creased by (+)-MK801. The inotropic effect of (+)-MK801was affected neither by α -antagonist(1μM prazosin)nor by β -adrenoceptor antagonist (3μM atenolol), butsignificantly by a transient outward K+ channel blocker(3 mM 4-aminopyridine). (+)-MK801 did not cause anysignificant change of intracellular cAMP content. Electro-physiological study in rat ventricular cells revealed that(+)-MK801 concentration-dependently prolonged the ac-tion potential duration with a concomitant decrease inthe maximum rate of the action potential upstroke (V )and an increase in the recovery time constant of V .Voltage clamp study showed that (+)-MK801 (3μM)re-duced inward Na+ current (I ), along with a slowing ofits recovery from inactivation and a slight negative shiftof its voltage-dependent steady-state inactivationcurves. At a much higher concentration (30μM), (+)-MK801 slightly reduced the amplitude of L-type calciuminward current (I ), although the voltage dependence ofits steady-state inactivation was unaffected. For the po-tassium currents in rat ventricular cells, 3μM of (+)-MK801 reduced the peak transient outward current (I ),steady-state outward current(I ) and inward currentthrough K channels. The inhibition of I was associatedwith a prominent negative shift in the voltage depen-dence of its steady-state inactivation curve. The outwardcurrent through K channels was unaffected. These re-sults indicate that (+)-MK801 may be a strong I and I blocker with some l blocking activity. The inhibition ofI and other K+ efflux would prolong action potentialduration, produce positive inotropic action and contrib-ute to the negative chronotropic effect of (+)-MK801.
- 中文關鍵字: --
- 英文關鍵字: Chronotropic effect. Inotropic effect.(+)-MK801. Action potential. Membrane current. Cardiomyocyte