钙通道阻滞药及肾素血管紧张素药理
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第22章 钙通道阻滞药 P203
(calcium channel blockers) －钙拮抗药(calcium antagonists)
❖概述 ➢复习生理知识 ➢钙通道阻滞药定义（熟悉） ➢钙通道和钙离子（了解） ➢钙通道阻滞药的分类（了解） ❖钙通道阻滞药的作用方式（自学） ❖钙通道阻滞药（掌握）
Na+ Positive Inward
Inward
Depolarization
Ca++ Positive Inward
Inward
Depolarization
K+ Positive Outward
Outward
Repolarization
Cl- Negative Inward
Outward
Repolarization
transients.
电压依赖的钙通道 根椐其电导值及动力学特性
L
N
T
P
Q
R
心血管系统，以L型为最重要
参与 L型
心肌 平滑肌 窦房结 房室结
传导 的主要通道
Main Functions of L-Type Ca++ Channels in the CV System
Cardiac action potential generation and propagation
(AV-conduction)
Excitation-contraction coupling in the heart
Vascular contraction
Regulation of pacemaker activity
Main Functions of T-type Ca++ Channels in the CV system
(receptor operated calcium channel，ROC) (2)电压依赖的钙通道 （voltage dependent calcium channel，VDC）
Function of Voltage-Gated Ca++ Channels
Mediate Ca++ influx in response to membrane depolarization
Intra- and Extra-Cellular Ion Concentrations
Life’s chemistry of aqueous solution employs ions as charge carriers which by crossing cell membranes generate electrical currents that signal cellular functions (contractility, secretion).
[Na+]o = 140 mM [Ca++]o = 2 mM [K+]o = 4 mM
++++++++++ _________
[Cl-]o = 140 mM
+++ __
+++++ +
___
___ +++++ +
[Na+]i = 10 mM
[Cl-]i = 15 mM
[Ca++]i = 0.001 mM [K+]i = 140 mM
Cellular Sites Regulating Intracellular Ca++ Concentration
VOC
Ca++ Na+ ROC
Ca++
SR Ca++
Na+ Ca++ MITO Ca++
Ca++
Ca++
In principle, all these Ca ++ sites are candidates for interactions with specific categories of drugs, but, in practice, the availability of therapeutically useful agents is thus far confined to blockers of voltage-gated Ca++ channels (VOC).
Contraction
Gene expression
Regulation of intracellular processes
Neurotransmission
Secretion
The entry of Ca++ into the cell is coupled to many cellular responses whereas the flow of Na+ and K+ across cell membranes is mainly linked to alterations in membrane potentials. Thus, Ca++ channels electrical signals are transduced by the cell into physiologically relevant Ca++
Myofibril
Plasma membrane
Inside
__________
+ ++++++++++
Outside
+பைடு நூலகம்
Ions as Charge Carriers across Cell Membranes
Ion
Charge
Direction of passive flux
Current generated
Effect on membrane potential
N-type and P-type Ca2+ channels mediate neurotransmitter release in neurons
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
postsynaptic cell
Skeletal muscle relies on intracellular Ca2+ for contraction
一、钙通道阻滞药的定义
选择性作用于电压依赖性钙通道，抑制Ca2+进入细 胞内，降低细胞内Ca2+浓度，影响细胞功能的药物。
二、钙离子的生理意义 （1）神经细胞的兴奋性 （2）神经递质的释放 （3）肌肉收缩（包括心肌、平滑肌、骨骼肌） （4）腺体分泌 （5）细胞的运动
二、钙通道
1、钙通道的类型
根椐激活方式的不同分二类 (1)受体调控的钙通道
(calcium channel blockers) －钙拮抗药(calcium antagonists)
❖概述 ➢复习生理知识 ➢钙通道阻滞药定义（熟悉） ➢钙通道和钙离子（了解） ➢钙通道阻滞药的分类（了解） ❖钙通道阻滞药的作用方式（自学） ❖钙通道阻滞药（掌握）
Na+ Positive Inward
Inward
Depolarization
Ca++ Positive Inward
Inward
Depolarization
K+ Positive Outward
Outward
Repolarization
Cl- Negative Inward
Outward
Repolarization
transients.
电压依赖的钙通道 根椐其电导值及动力学特性
L
N
T
P
Q
R
心血管系统，以L型为最重要
参与 L型
心肌 平滑肌 窦房结 房室结
传导 的主要通道
Main Functions of L-Type Ca++ Channels in the CV System
Cardiac action potential generation and propagation
(AV-conduction)
Excitation-contraction coupling in the heart
Vascular contraction
Regulation of pacemaker activity
Main Functions of T-type Ca++ Channels in the CV system
(receptor operated calcium channel，ROC) (2)电压依赖的钙通道 （voltage dependent calcium channel，VDC）
Function of Voltage-Gated Ca++ Channels
Mediate Ca++ influx in response to membrane depolarization
Intra- and Extra-Cellular Ion Concentrations
Life’s chemistry of aqueous solution employs ions as charge carriers which by crossing cell membranes generate electrical currents that signal cellular functions (contractility, secretion).
[Na+]o = 140 mM [Ca++]o = 2 mM [K+]o = 4 mM
++++++++++ _________
[Cl-]o = 140 mM
+++ __
+++++ +
___
___ +++++ +
[Na+]i = 10 mM
[Cl-]i = 15 mM
[Ca++]i = 0.001 mM [K+]i = 140 mM
Cellular Sites Regulating Intracellular Ca++ Concentration
VOC
Ca++ Na+ ROC
Ca++
SR Ca++
Na+ Ca++ MITO Ca++
Ca++
Ca++
In principle, all these Ca ++ sites are candidates for interactions with specific categories of drugs, but, in practice, the availability of therapeutically useful agents is thus far confined to blockers of voltage-gated Ca++ channels (VOC).
Contraction
Gene expression
Regulation of intracellular processes
Neurotransmission
Secretion
The entry of Ca++ into the cell is coupled to many cellular responses whereas the flow of Na+ and K+ across cell membranes is mainly linked to alterations in membrane potentials. Thus, Ca++ channels electrical signals are transduced by the cell into physiologically relevant Ca++
Myofibril
Plasma membrane
Inside
__________
+ ++++++++++
Outside
+பைடு நூலகம்
Ions as Charge Carriers across Cell Membranes
Ion
Charge
Direction of passive flux
Current generated
Effect on membrane potential
N-type and P-type Ca2+ channels mediate neurotransmitter release in neurons
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
postsynaptic cell
Skeletal muscle relies on intracellular Ca2+ for contraction
一、钙通道阻滞药的定义
选择性作用于电压依赖性钙通道，抑制Ca2+进入细 胞内，降低细胞内Ca2+浓度，影响细胞功能的药物。
二、钙离子的生理意义 （1）神经细胞的兴奋性 （2）神经递质的释放 （3）肌肉收缩（包括心肌、平滑肌、骨骼肌） （4）腺体分泌 （5）细胞的运动
二、钙通道
1、钙通道的类型
根椐激活方式的不同分二类 (1)受体调控的钙通道