生理学教学课件：第二章细胞的兴奋

1、chap. 2 The resting membrane potential chap. 3 Action potential 第二章第二章 细胞的兴奋细胞的兴奋 from Berne & Levy Principles of Physiology (4th ed) 2005 chap. 16 Electrical activity of the heart chap. 17 Natural excitation of the heart Observations of Membrane Potentials 4. ACTION PONTIELS 1. IONIC EQUILIBRIA 2.

2、RESTING MEMBRANE POTENTIALS 3. SUBTHRESHOLD RESPONSES 5. 心肌细胞和起搏细胞的动作电位心肌细胞和起搏细胞的动作电位 Luigi Galvani (1737-1798) Observations of Membrane Potentials Extracellular recording Helmholtz测量出神经信号的传导速度测量出神经信号的传导速度 Intracellular recording Voltage clamp macroscopical current Patch clamp single channel current

3、 1. IONIC EQUILIBRIA Concentration force Electrical force 在选择性通透膜上建立的平衡在选择性通透膜上建立的平衡 Electrochemical Equilibrium When the force caused by the concentration difference and the force caused by the electrical potential difference are equal and opposite, no net movement of the ion occurs, and the ion is

4、 said to be in electrochemical equilibrium across the membrane. When an ion is in electrochemical equilibrium, the electrochemical potential difference is called as equilibrium potential or Nernst potential. The Nernst Equation B A BAX X X zF RT EEE ln Where EXequilibrium potential of X+ Rideal gas

5、constant Tabsolute temperature zcharge number of the ion FFaradays number natural logarithm of concentration ration of X+on the two sides of the membrane B A X X ln At any membrane potential other than the Ex , there will be an electrochemical driving force for the movement of X+ across the membrane

6、, which tend to pull the membrane potential toward its EX. The greater the difference between the membrane potential and the EX will result in a greater driving force for net movement of ions. Movement can only happen if there are open channels! Distribution of Ions Across Plasma Membranes of a huma

7、n skeletal muscle cell 神经元神经元 胞内的钾离子浓度高胞内的钾离子浓度高 胞外的钠、氯、钙离子浓度高胞外的钠、氯、钙离子浓度高 2. RESTING MEMBRANE POTENTIALS The cytoplasm is usually electrically negative relative to the extracellular fluid. This electrical potential difference across the plasma membrane in a resting cell is called the resting membr

8、ane potential. The Chord Conductance Equation Cl Cl Na Na K K m E g g E g g E g g E where Emmembrane potential Esequilibrium potentials of the ion s gsconductance of the membrane to the ion s. the more permeable, the greater the conductance. ClNaK gggg The Na+,K+-ATPase contributes directly to gener

9、ation of the resting membrane potential. All the ions that the membrane is permeable to contribute to the establishment of the potential of the membrane at rest. 细胞膜在静息状态下对细胞膜在静息状态下对K+的通透性一般大于其的通透性一般大于其 它离子（主要是它离子（主要是IK1），因此大多数细胞的静息膜），因此大多数细胞的静息膜 电位都是胞内为负。电位都是胞内为负。 3. SUBTHRESHOLD RESPONSES The size

10、 (amplitude) of the subthreshold potential is directly proportional to the strength of the triggering event. A subthreshold potential can be either hyperpolarizing (make membrane potential more negative) or depolarizing (make membrane potential more positive) graded potential This passive spread of

11、electrical signals with no changes in membrane property is known as electrotonic conduction. Subthreshold potentials decrease in strength as they spread from their point of origin, i.e. conducted with decrement. local response spatial summation & temporal summation 4. ACTION PONTIELS An action poten

12、tial is a rapid change in the membrane potential followed by a return to the resting membrane potential. action potential of a squid giant axon At peak of action potential membrane potential reverses from negative to positive (overshoot). During the hyperpolarizing afterpotential, the membrane poten

13、tial actually becomes less negative than it is at rest. Rising phase (depolarization phase) Repolarization phase An action potential is triggered when the depolarization is sufficient for the membrane potential to reach a threshold. Ionic Mechanisms of Action Potential Nam Na Na EE I g Km K K EE I g

14、 changes of ion conductance during action potential Action potentials arise as a result of brief alterations in the electrical properties of the membrane. During the early part of the action potential, the rapid increase in gNa causes the membrane potential to move toward ENa. The rapid return of th

15、e action potential toward the resting potential is caused by the rapid decrease in gNa and the continued increase in gK. Action potentials differ in size and shape in different cells, but the fundamental mechanisms underlying the initiation of these potentials does not vary. During the hyperpolarizi

16、ng afterpotential, when the membrane potential is actually more negative than the resting potential, gNa returns to baseline levels, but gK remains elevated above resting levels. model of the voltage-dependent Na+ channel closed open inactivated 去极相：去极相： INa激活，钠内流激活，钠内流 枪乌贼巨轴突动作电位各个时期的主要电流枪乌贼巨轴突动作电位

17、各个时期的主要电流 超级化后电位：超级化后电位： 膜电位复极到静息电位时，膜电位复极到静息电位时，IK仍然开放，钾继仍然开放，钾继 续外流使得膜电位超级化；续外流使得膜电位超级化； 随着随着IK的缓慢关闭，膜电位逐渐回到静息电位。的缓慢关闭，膜电位逐渐回到静息电位。 复极相：复极相： INa失活；失活；IK激活，激活，钾外流钾外流 Either a stimulus fails to elicit an action potential or it produces a full-sized action potential. Properties of Action Potential Al

18、l-or-None Response The size and shape of an action potential remain the same as the potential travels along the cell. The intensity of a stimulus is encoded by the frequency of action potentials. Refractory Period relative refractory period absolute refractory period Conduction of Action Potential L

19、ocal circuit current Self-reinforcing myelinatio n Conduction velocity diameter saltatory conduction 5. 细胞动作电位的多态性细胞动作电位的多态性 心脏中两种细胞的动作电位心脏中两种细胞的动作电位 心肌细胞心肌细胞 起搏细胞起搏细胞 心肌细胞动作电位的波形心肌细胞动作电位的波形 4期：静息期期：静息期 0期：快速去极化期期：快速去极化期 -90mV to +30mV,12ms 1期：快速复极化初期期：快速复极化初期 +30mV to 0mV, 10ms 2期：平台期期：平台期 0mV, 100

20、150ms 3期：快速复极化末期期：快速复极化末期 0mV to -90mV, 100150ms 心肌细胞动作电位的离子机制心肌细胞动作电位的离子机制 心肌细胞动作电位不同时期的主要离子通道心肌细胞动作电位不同时期的主要离子通道 IK1：内向整流钾通道：内向整流钾通道 INa：快钠通道：快钠通道 激活和失活的速率很快激活和失活的速率很快 Ica,L：L型钙通道型钙通道 激活电位约激活电位约-30mV，激活速度较慢，激活速度较慢( 约约20ms)， 失活速度很慢失活速度很慢(约约500ms) Ito：瞬时外向钾通道：瞬时外向钾通道 激活（约激活（约2ms）和失活（）和失活（20ms）都相对较）都相对较 快快 IK：延迟整流钾通道：延迟整流钾通道 缓慢激活和失活（缓慢激活和失活（2001000ms），）， 激活后电流随膜电位呈现整流性质激活后电流随膜电位呈现整流性质 心肌细胞动作电位各个时期的主要电流心肌细胞动作电位各个时期的主要电流 1期：快速复极化初期期：快速复极化初期 INa失活；失活；Ito激活，激活，钾外流钾外流 0期：快速去极化期期：快速去极化期 INa激活，钠内流；激活，钠内流； IK1电流减小电流减小 3期：快速复极化末期期：快速复极化