1calciumblock

1、cardiovascular pharmacologychina medical university ren jie tel: 5317 room: 333email: k k+ +、nana+ +、caca2+2+等等选择通透选择通透细细胞生物电活动胞生物电活动 特性：特性：研究技术：研究技术： 膜片钳技术和分子克隆技术膜片钳技术和分子克隆技术patch clamp 膜片钳the nobel prize in physiology or medicine (1991)1. no gating channels (background channel)2. gating channels 按

2、激活方式分按激活方式分 1. 1. 电压门控离子通道电压门控离子通道（voltagevoltage gated channels/ vdc) gated channels/ vdc) 2. 2. 化学门控离子通道化学门控离子通道（ligandligand gated channels) gated channels) 3. 3. 机械敏感离子通道机械敏感离子通道（m mechanically gated ion echanically gated ion channels)channels)按离子选择性分按离子选择性分 钠通道gating channels(参见参见p27图图24-1)inac

3、tive stateaiaaiia: activation gate i: inactivation gategating只有在经过从只有在经过从失活关闭状态失活关闭状态进进入静息关闭状态入静息关闭状态后，通道后，通道才能再度接受外界刺激而激才能再度接受外界刺激而激活开放。活开放。inactive statemolecular structure of vdcmolecular structure of vdc , , , , et al subunit, et al subunit, 亚基的四个跨膜区（亚基的四个跨膜区（d1-d4） 6 transmembrane segments, s1-

4、s6） s1 s2 s3 s5 s6 s4 电压感受器（电压感受器（voltage sensor） 孔道区（孔道区（pore region） they are classified into 6 subtypes：cardiovascular systemiiiiviiiiviii5656outin i ii iii ivthe calcium channel blockers inhibit the passage of calcium through the voltage gated l-type channels of smooth and cardiac muscle membran

5、e, reduce cytoplasmic free calcium concentration and cause the muscle to relax. 、nicardipine 、 nitrendipine、amlodipine、nimodipine diltiazem、clentiazem 、 diclofurine prenylamine， flunarizine 氟桂利嗪氟桂利嗪 1. actions on heart negative inotropic, negative chronotropic and negative dromotropic. pharmacologic

6、al actionsnegative inotropic action肌球蛋白肌球蛋白肌钙蛋白肌钙蛋白肌动蛋白肌动蛋白27肌动蛋白肌动蛋白原肌球蛋白原肌球蛋白肌钙蛋白肌钙蛋白a. 肌动蛋白（肌动蛋白（actin，肌纤蛋白），肌纤蛋白）b. .原肌球蛋白原肌球蛋白（tropomyosin，原肌疑蛋白），原肌疑蛋白）c. .肌钙蛋白肌钙蛋白（troponin）：）： c亚单位：与亚单位：与ca2+结合结合 t亚单位：亚单位： i 亚单位：亚单位：the 0 phase depolarization in sa and a-v nodes is largely ca2+ mediated.the r

7、ecovery process is delayed by verapamil and to a lesser extent by diltiazem but not by dhpsnegative chronotropic and dromotropic action automaticity and conductivity of these cells dependent on the rate of recovery of the ca2+ channel.l-typeslow response cells(sa node, av node)ca2+ca2+403 calcium ch

8、annel blockerssmooth muscle relaxation. important differences verapamil reducing calcium entry into cardiac and vascular cellsmainly block l-type calcium channels in vascular cells, nifedipinethe vascular smooth muscle has a more depolarized membrane (rmp about - 40 mv) than heart .ccbs bind to their own specific binding sites on the 1 subunitdiltiazem、amlodipine.nimodipinereduction in cardiac work: mainly as a result of reduced afterload. prevent arterial apasm, reduction of cardiac o2 demandnot a