1calciumblock

1、cardiovascular pharmacologychina medical university ren jie tel: 5317 room: 333email: k k+ +、nana+ +、caca2+2+等等選擇通透選擇通透細細胞生物電活動胞生物電活動 特性：特性：研究技術：研究技術： 膜片鉗技術和分子克隆技術膜片鉗技術和分子克隆技術patch clamp 膜片鉗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. 電壓門控離子通道電壓門控離子通道（voltagevoltage gated channels/ vdc) gated channels/ vdc) 2. 2. 化學門控離子通道化學門控離子通道（ligandligand gated channels) gated channels) 3. 3. 機械敏感離子通道機械敏感離子通道（m mechanically gated ion echanically gated ion channels)channels)按離子選擇性分按離子選擇性分 鈉通道gating channels(參見參見p27圖圖24-1)inac

3、tive stateaiaaiia: activation gate i: inactivation gategating只有在經(jīng)過從只有在經(jīng)過從失活關閉狀態(tài)失活關閉狀態(tài)進進入靜息關閉狀態(tài)入靜息關閉狀態(tài)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開放?；铋_放。inactive statemolecular structure of vdcmolecular structure of vdc , , , , et al subunit, et al subunit, 亞基的四個跨膜區(qū)（亞基的四個跨膜區(qū)（d1-d4） 6 transmembrane segments, s1-

4、s6） s1 s2 s3 s5 s6 s4 電壓感受器（電壓感受器（voltage sensor） 孔道區(qū)（孔道區(qū)（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鈣蛋白肌鈣蛋白肌動蛋白肌動蛋白27肌動蛋白肌動蛋白原肌球蛋白原肌球蛋白肌鈣蛋白肌鈣蛋白a. 肌動蛋白（肌動蛋白（actin，肌纖蛋白），肌纖蛋白）b. .原肌球蛋白原肌球蛋白（tropomyosin，原肌疑蛋白），原肌疑蛋白）c. .肌鈣蛋白肌鈣蛋白（troponin）：）： c亞單位：與亞單位：與ca2+結合結合 t亞單位：亞單位： i 亞單位：亞單位：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