Action Potential Excitable tissue – Nerve ,muscle contd….. Learning objectives • Recognize the Terminologies used in describing the Action Potential. • Describe the roles of Voltage gated Na+ channels and K+ channels in the generation of the action potential. • Describe and plot action potential • Discuss the relative kinetics of Na+, Ca2+, and K+ channel gating. • List properties of action potential. • Describe how changes in serum calcium affect the nerve action potential. Terminology • The usual resting membrane potential is oriented with the cell interior negative. • Depolarization: it’s the process of making the membrane potential LESS NEGATIVE • Depolarization makes the interior of the cell less negative, or it may even cause the cell interior to be positive. • Hyperpolarization: is the process of making the membrane potential more negative • Threshold potential : it’s the membrane potential at which occurrence of the AP is inevitable. • The threshold potential is less negative than the resting membrane potential (an inward current is needed for this to happen) • At threshold potential, the net inward current becomes larger than the net outward current to sustain the threshold. Action potential The sequence of rapid changes in the membrane potential that spread rapidly along the nerve fiber when a threshold stimulus is applied following its restoration to the resting level is called action potential Action potential is a property of excitable cells (i.e., nerve, muscle) that consists of a rapid depolarization, or upstroke, followed by repolarization of the membrane potential. • Overshoot: that portion of the AP where the membrane potential is positive (cell interior positive) • Undershoot: is that portion of the AP, following repolarization where the membrane potential is more negative than at rest. 1. VOLTAGE GATED Na⁺ AND K⁺ CHANNELS Voltage gated Na⁺ channels ↙ ↘ Activation gate (outside) Inactivation gate( inside ) Delayed 10,000 of a sec. close at R M P. Conformationalchange increases permeability by 500–5000 times 2. Voltage gated K⁺ channels Opening corresponds with the closure of Na⁺ gates 3. Other ions : Ca⁺ Ca⁺pump acts along with Na⁺ pump in heart and smooth muscle Voltage gated Ca⁺ channel – slow VOLTAGE GATED NA AND K CHANNELS Generation of Action Potential • Tetrodotoxin (TTX) and lidocaine block these voltage-sensitive Na+ channels and abolish action potentials. overshoot is the brief portion at the peak of the action potential when the membrane potential is positive undershoot Action Potentials • PHASES: • threshold excitation (depolarisation) • rising phase • falling phase (Repolarisation) • undershoot (hyperpolarisation) Membrane Conductance • Definition: Membrane conductance refers to the number of channels that are open in a membrane. • For example, Na+ conductance is proportional to the number of open channels that will allow the Na+ to pass through the membrane. • General properties If conductance is increasing, channels are opening, and if conductance is decreasing, channels are closing. • The rate at which ions move across a membrane depends on the number of open channels and the net force. When ions flow through channels, the cell’s membrane potential changes. However, under physiologic conditions, too few ions flow to produce a significant effect on the ion’s extracellular concentration or the concentration gradient across the membrane. • Inward current is the flow of positive charge into the cell. Inward current depolarizes the membrane potential • Outward current is the flow of positive charge out of the cell. Outward current hyper polarizes the membrane potential Cadiac muscle Action Potential Smooth Muscle Action potential Membrane potential (mV) Action potential 0 Ca2+ influx K+ efflux -45 Threshold of VOC’s -50 200 msec Characteristics of an AP 1. Stereotypical size and shape 2. Refractory period 3. Propagation 4. All or none response 1.Stereotypical size and shape • Stereotypical size and shape: Each normal action potential for a given cell type looks identical, depolarizes to the same potential, and repolarizes back to the same resting potential. Types & duration of AP 1.Spike potential (Nerve fibre ,skeletal muscle ) – 10 to 50m sec 2.Plateau type (Myocardial cell & smooth muscle cell ) – 250 to 350m sec 3.Pace maker type (Conducting system of heart & smooth muscle fibres ) – 100 to 150m sec 2. Refractory period • Refractory period: the period during which another normal action potential cannot be elicited in an excitable cell. • Refractory periods can be absolute or relative. Refractory period Absolute refractory period (functional refractory period)-- Relative refractory period- • The absolute refractory period is that period during which no matter how strong the stimulus, it cannot induce a second action potential • The relative refractory period is that period during which a greater than normal stimulus is required to induce a second action potential. 31 3. Accommodation • When a nerve or muscle cell is depolarized slowly or is held at a depolarized level, the usual threshold potential may pass without an action potential having been fired called accommodation. • occurs because depolarization closes inactivation gates on the Na+ channels and if depolarization occurs slowly enough, the Na+ channels close and remain closed. • Example: is demonstrated in hyperkalemia, in which skeletal muscle membranes are depolarized by the high serum K+ concentration. Although the membrane potential is closer to threshold, action potentials do not occur because inactivation gates on Na+ channels are closed by depolarization, causing muscle weakness. The voltage-gated sodium channels have two gates: 1. A voltage-sensitive gate opens as the cell is depolarized. 2. A second, time-sensitive inactivation gate stops the movement of sodium through the channel after the channel has been open for a certain time Depolarization closes inactivation gates on the Na+ channels 4. Propagation of action potentials • Occurs by the spread of local currents to adjacent areas of membrane, which are then depolarized to threshold and generate action potentials Propagation: • Propagation: An action potential at one site causes depolarization at adjacent sites, bringing those adjacent sites to threshold. Propagation of action potentials from one site to the next is nondecremental. Initiation & propagation of AP Factors affecting: Conduction Velocity of the Action Potential . Size of the action potential: • Cell diameter: • Myelin: The greater the myelination, the greater the conduction velocity. • (Demyelination (e.g., multiple sclerosis, Guillain-Barre syndrome): This would decrease the amplitude of the action potential as it travels from node to node. If the action potential arrives below a certain magnitude, another action potential may not be generated and transmission is blocked.) • Thus, Large myelinated fibers =fast conduction All or none response---Either the AP occurs or does not occur. • All-or-none response: An action potential either occurs or does not occur. If an excitable cell is depolarized to threshold in a normal manner, then the occurrence of an action potential is inevitable. If the membrane potential has not reached the threshold, no action potential can occur. Local Anesthetics. Among the most important stabilizers are the many substances used clinically as local anesthetics, including procaine and tetracaine. Most of these act directly on the activation gates of the sodium channels, making it much more difficult for these gates to open, thereby reducing membrane excitability. For a television game show, 16 contestants volunteer to be stranded on a deserted island in the middle of the South China Sea. They must rely on their own survival instincts and skills. During one of the challenges, one team wins a fishing spear. They catch a puffer fish and cook it over the open flames of their barbecue. None of them are very skilled in cooking, but they enjoy the fish anyway. One of the contestants, a worldwide traveler, comments that it tastes like Fugu. After dinner, they all develop a strange tingling around their lips and tongue. They all become weak, and their frailty progresses to paralysis. They all die. What was the cause of death? A B C D E Tetrodotoxin Botulism Bacillus cereus food poisoning Tetanus Ciguatoxin A well-meaning third year medical student accidentally pushes an unknown quantity of KCl IV to a patient. If the concentration of potassium outside a neuron were to increase from 4 mEq/L to 8 mEq/L, what would you expect to happen to the minimal stimulus required for initiation of an action potential? A The minimal stimulus required for initiation of an action potential would remain the same B The minimal stimulus required for initiation of an action potential would increase C The minimal stimulus required for initiation of an action potential would decrease D The minimal stimulus required for initiation of an action potential would stay the same, but the amplitude of the peak of the action potential would increase E The minimal stimulus required for initiation of an action potential would stay the same, but the conduction velocity of the action potential down an axon would slow If the extracellular K+ concentration is increased from 4 meq/L to 10 meq/L • a. The membrane potential will become more negative • b. The sodium conductance will increase • c. The potassium conductance will increase • d. The membrane will become more excitable • e. The Na-K pump will become inactivated Q : During the upstroke of the nerve action potential (A) there is net outward current and the cell interior becomes more negative (B) there is net outward current and the cell interior becomes less negative (C) there is net inward current and the cell interior becomes more negative (D) there is net inward current and the cell interior becomes less negative At which point on the action potential does the Na+current exceed theK+ current? a. Point A b. Point B c. Point C d. Point D e. Point E At which point on the action potential is the membrane closest to theNa+ equilibrium potential? a. Point A b. Point B c. Point C d. Point D e. Point E