Membrane Potentials and Action Potentials Introduction PDF

Membrane Potentials and Action Potentials What is membrane potential? Membrane potential is the difference in electrical potential between the intracellular fluid and the extracellular fluid of a biological cell. Typical values of membrane potential range from –40 mV to –80 mV. Why there is mem...

Membrane Potentials and Action Potentials What is membrane potential? Membrane potential is the difference in electrical potential between the intracellular fluid and the extracellular fluid of a biological cell. Typical values of membrane potential range from –40 mV to –80 mV. Why there is membrane potential? The intracellular fluid (cytosol) and extracellular fluid differ markedly in ionic composition. The extracellular fluid (ECF) contains high concentrations of sodium ions (Na+) and chloride ions (Cl–), whereas the cytosol contains high concentrations of potassium ions (K+) and negatively charged proteins. These passive and active mechanisms do not ensure the equal distribution of charges across the cell membrane. Membrane permeability varies by ion. For example, negatively charged proteins inside the cell cannot cross the membrane, and it is easier for K+ to diffuse out of the cell through a potassium channel than it is for Na+ to enter the cell through a sodium channel. As a result, the inner surface has an excess of negative charges with respect to the outer surface. Resting potential When the membrane potential of a cell can go for a long period of time without changing significantly, in the absence of excitation, it is referred to as a resting potential or resting voltage. The resting membrane potential of large nerve fibers. when not transmitting nerve signals is about –90 millivolts, that is due to 1. Presence of Na-K pump 2. High cell permeability for K due to the leakage of K and Na through the cell membrane. 3. High concentration of protein  Resting Membrane Potential of Nerves 1. Primary Active Transport Sodium-Potassium Pump Inside the cell are large numbers of proteins and other organic molecules that cannot escape from the cell. Most of these are negatively charged and therefore attract large numbers of potassium, sodium, and other positive ions as well (The cell will swell). The normal mechanism for preventing this is the Na+K+ pump. 2. Leakage of Potassium and Sodium Through the Nerve Membrane The membrane is far less permeable to sodium ions than to potassium ions, this differential in permeability is exceedingly important in determining the level of the normal resting membrane potential.  The concentration of major electrolyte in body fluid (mmol/L). Electrolyte ECF ICF Na 145 10 K+ 11 142 Ca+ 5 1 Mg+ 2 40 Anions Cl- 110 105 HCO3- 28 10 Protein - 17 45 HPO4- 6 196 Type of stimulus channels Based on the stimulus to which they respond, ion channels are divided into three superfamilies: (1) Voltage-gated channel ✓ Voltage-gated Na+ channel ✓ Voltage-dependent calcium channels (VDCC): Are a group of voltage-gated ion channels found in excitable cells ( muscle, neurons, etc.) with a permeability to the ion Ca2+.These channels are slightly permeable to sodium ions, so they are also called Ca2+-Na+ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions. (At physiologic or resting membrane potential, VDCCs are normally closed). ✓ Voltage-gated K+ channels. ✓ Voltage-gated Cl- channels (2) Ligand-gated They are named according to the ligand to which they respond (3)Mechano-sensitive ion channels. Ion Channels The ion channels in the postsynaptic neuronal membrane are usually of two types: (1) Cation channels That most often allow sodium ions to pass when opened, but sometimes allow potassium and/or calcium ions as well. (2) Anion channels That allow mainly chloride ions to pass but also minute quantities of other anions. Nerve Action Potential When the membrane potential becomes less negative than during the resting state, rising from –90 millivolts toward zero. This is called the action potential. The necessary actor in causing both depolarization and repolarization of the nerve membrane during the action potential is the voltage-gated sodium channel. A voltage-gated potassium channel also plays an important role in increasing the rapidity of repolarization of the membrane. During this state, sodium ions can pour inward through the channel, increasing the sodium permeability of the membrane as much as 500- to 5000-fold. Nerve signals are transmitted by action potential, which are rapid changes in the membrane potential that spread rapidly along the nerve fiber membrane. To conduct a nerve signal, the action potential moves along the nerve fiber until it comes to the fiber’s end. The successive stages of the action potential of nerve are: Resting Stage This is the resting membrane potential before the action potential begins. The membrane is said to be “polarized” during this stage because of the negative membrane potential is –90 millivolts. Depolarization Stage At this time, the membrane suddenly becomes very permeable to sodium ions, in large nerve the membrane potential to be counted to actually “overshoot”, where as in small nerve the potential approaches the zero level and does not overshoot to the positive state Repolarization Stage. The sodium channels begin to close and the potassium channels open more than normal.  Refractory Period A new action potential cannot occur in an excitable fiber as long as the membrane is still depolarized from the preceding action potential. The reason for this is that, the sodium channels become inactivated, and no amount of excitatory signal applied to these channels The period during which a second action potential cannot be elicited, even with a strong stimulus, is called the absolute refractory period. This period for large myelinated nerve fibers is about 1/2500 second Nervous System(NS) Neuron Structure Neurons vary in appearance, but all of them have just three parts: a cell body, dendrite(s), and an axon. Any long axon is also called a nerve fiber. Long axons are covered by a white myelin sheath a neuroglia cell (Schwann cell) performs this function, leaving gaps called (Nodes of Ranvier). Schwann cell is another type of neuroglial cell performs a similar function in the CNS. Transmit nerve impulses “Saltatory” Conduction in Myelinated Fibers from Node to Node: Conduction of an action potential in a myelinated axon distinguish by that, action potential jumps from one neurofibril node to the next along the axon. This makes the speed of a nerve impulse much faster than in unmyelinated axons (0.25m/sec, 100m/sec). Almost all axons are myelinated in humans. The impulses of action potential in nonmyelinated nerve called continuous conduction. Types of Neurons Neurons can be classified according to their function and shape. 1. Sensory neurons take nerve impulses from sensory receptors to the CNS. The sensory neuron it may be a part of a highly complex organ, such as the eye. (Fig.b). 2. Motor neurons take nerve impulses from the CNS to muscles or glands. Motor neurons are said to be multipolar because they have many dendrites and a single axon (Fig. a). 3. Interneurons, occur entirely within the CNS (Fig. c), Some lie between sensory neurons and motor neurons, and some take messages from one side of the spinal cord to the other or from the brain to the Cord. They also form complex pathways in the brain where processes accounting for thinking, memory, and language occur. Synapse structure and function. The Synapse formed by the terminal end of axon with another nerve cell, gland or muscle Types of Synapses There are two major types of synapses: (a) The electrical synapse (b) The chemical synapse (a) Electrical synapses, In contrast, are characterized by direct open fluid channels that conduct electricity from one cell to the next. Most of these consist of small protein tubular structures called gap junctions that allow free movement of ions from the interior of one cell to the interior of the next. Only a few examples of gap junctions have been found in the central nervous system. Example of electrical synapses are transmitted from one smooth muscle fiber to the next in visceral smooth muscle and from one cardiac muscle cell to the next in cardiac muscle (b) The chemical synapse (“One-Way” Conduction ): Transmission across a synapse from one neuron to another or from neuron to gland or muscle occurs when a neurotransmitter is released at the presynaptic membrane, diffuses across a synaptic cleft, and binds to a receptor in the postsynaptic membrane. Transmission across a synapse is carried out by molecules called neurotransmitters, which are stored in synaptic vesicles in the axon terminal.  More than 40 important transmitter substances have been discovered. Some of the best known are acetylcholine, norepinephrine, epinephrine, histamine, glycine, serotonin, and glutamate. When nerve impulses traveling along an axon reach an axon terminal, channels for calcium ions open, and calcium enters the terminal. This sudden rise in Ca stimulates synaptic vesicles to merge with the presynaptic membrane, and neurotransmitter (NT) molecules are released into the synaptic cleft. The NT diffuse across the cleft to the postsynaptic membrane, where they bind with specific receptor proteins and make an action potential Some Special Characteristics of Synaptic Transmission Fatigue of Synaptic Transmission is a protective mechanism against excess neuronal activity. Acidosis or Alkalosis affect on Synaptic transmission. Normally, alkalosis greatly increases neuronal excitability. Conversely, acidosis greatly depresses neuronal activity; a fall in pH from 7.4 to below 7.0 usually causes a comatose state. Effect of Hypoxia on Synaptic Transmission. Neuronal excitability is also highly dependent on an adequate supply of oxygen. Many drugs are known to increase the excitability of neurons, and others are known to decrease excitability. For instance, caffeine which are found in coffee, tea, and cocoa, respectively, all increase neuronal excitability. Most anesthetics decrease synaptic transmission at many points in the nervous system. Electrical Events During Neuronal excitability Excitatory Postsynaptic Potential (EPSP) 1. Opening of sodium channels to allow large numbers of positive electrical charges to flow to the interior of the postsynaptic cell. 2. Depressed conduction through chloride or potassium channels, or both. This decreases the diffusion of negatively charged chloride ions to the inside of the postsynaptic neuron 3. Various changes in the internal metabolism of the postsynaptic neuron to excite cell activity or to increase the number of excitatory membrane receptors or decrease the number of inhibitory membrane receptors. Electrical Events During Neuronal Inhibition Inhibitory Postsynaptic Potential (IPSP) Opening the chloride channels will allow negatively charged chloride ions to move from the extracellular fluid to the interior, which will make the interior membrane potential more negative. GABA (gamma- aminobutyric acid) has a specific effect of opening anion channels, allowing large numbers of chloride ions to diffuse into the terminal fibril Opening potassium channels will allow positively charged potassium ions to move to the exterior, and this will also make the interior membrane potential more negative than usual. Inhibition of Excitability— “Stabilizers” and Local Anesthetics In contrast to the factors that increase nerve excitability, still others, called membrane- stabilizing factors, can decrease excitability. For example, a high extracellular fluid calcium ion concentration decreases membrane permeability to sodium ions and simultaneously reduces excitability. Therefore, calcium ions are said to be a “stabilizer.” 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. Chemical Substances That Function as Synaptic Transmitters The most important of the small-molecule transmitters are the following 1) Acetylcholine: This transmitter substance is synthesized in the presynaptic terminal from acetyl coenzyme A and choline in the presence of the enzyme choline acetyltransferase. When the vesicles later release the acetylcholine into the synaptic cleft during synaptic neuronal signal transmission, the acetylcholine is rapidly split again to acetate and choline by the enzyme cholinesterase, which is present in the space of the synaptic cleft. Acetylcholine is secreted by neurons in many areas of the nervous system but specifically by (1) the terminals of the large pyramidal cells from the motor Cortex. (2) the motor neurons that innervate the skeletal muscles. (3) the preganglionic neurons of the autonomic nervous system. (4) the postganglionic neurons of the parasympathetic nervous system, and (5) some of the postganglionic neurons of the sympathetic nervous system. 2) Norepinephrine: synthesis from Tyrosine and is secreted by the terminals of many neurons in the brain. Norepinephrine is secreted by most postganglionic neurons of the sympathetic nervous system and it activates excitatory receptors. After secretion of norepinephrine, it is removed from the secretory site in three ways: (1) reuptake into the adrenergic nerve endings by an active transport process (50 to 80%), (2) diffusion away from the nerve endings into the surrounding body fluids and then into the blood and (3) destruction of small amounts by tissue enzymes (monoamine oxidase, which is found in the nerve endings, and another is catechol-O-methyl transferase which is present in all tissues) 3) Dopamine: is secreted by neurons that originate in the basal ganglia of the brain. The effect of dopamine is usually inhibition. 4) Glycine: is secreted mainly at synapses in the spinal cord. It is believed to always act as an inhibitory transmitter. 5) GABA(gamma-aminobutyric acid): is secreted by nerve terminals in the spinal cord, cerebellum, basal ganglia, and many areas of the cortex. It is believed always to cause inhibition. 6) Glutamate: is secreted by the presynaptic terminals in many of the sensory pathways entering the central nervous system. It probably always causes excitation. 7) Serotonin: is secreted by nuclei in the brain stem and spinal cord areas, Serotonin acts as an inhibitor of pain pathways in the cord, and an inhibitor action in the higher regions of the nervous system is believed to help control the mood of the person, perhaps even to cause sleep. 8) Nitric oxide: is especially secreted by nerve terminals in areas of the brain responsible for long- term behavior and for memory. it is synthesized almost instantly as needed. All-or-Nothing Principle Once an action potential has been elicited at any point on the membrane of a normal fiber, the depolarization process travels over the entire membrane if conditions are right, or it does not travel at all if conditions are not right General Design of the Nervous System 1. Sensory Part of the Nervous System—Sensory Receptors :Most activities of the nervous system are initiated by sensory experience exciting sensory receptors, whether visual receptors in the eyes, auditory receptors in the ears, tactile receptors on the surface of the body, or other kinds of receptors. 2. Motor Part of the Nervous System—Effectors: The most important eventual role of the nervous system is to control the various bodily activities. This is achieved by controlling (1) contraction of skeletal muscles (2) contraction of smooth muscle in the internal organs, and (3) secretion of exocrine and endocrine glands. These activities are collectively called motor functions of the nervous system