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Membrane Transport and Membrane Potentials Dr. Michael P. Gillespie Action Potential Have the ability to produce action potentials or impulses (electrical excitability) in response to a stimulus. An action potential is an electrical signal that propagates from one point to the next along the plasma membrane of a neuron. A stimulus is any change in the environment that is strong enough to initiate an action potential. Parts of a Neuron Cell Body Dendrites Axon Parts of a Neuron (Cell Body) Cell body (perikaryon or soma). Contains the nucleus surrounded by cytoplasm which contains the organelles. Clusters of rough ER called Nissl bodies (produce proteins to grow and repair damaged nerves) Parts of a Neuron (Nerve Fiber) Nerve fiber – any neuronal process that emerges from the cell body of a neuron. Dendrites Axon Parts of a Neuron (Dendrites) Dendrites (= little trees). The receiving (input) portion of a neuron. Short, tapering, and highly branched. Parts of a Neuron (Axon) Axon (= axis). Each nerve contains a single axon. The axon propagates nerve impulses toward another neuron, muscle fiber, or gland cell. Long, thin, cylindrical projection that often joins the cell body at a coneshaped elevation called the axon hillock (= small hill). The part of the axon closest to the hillock is the initial segment. The junction between the axon hillock and the initial segment is the trigger zone (nerve impulses arise here). The cytoplasm of the axon is the axoplasm and is surrounded by a plasma membrane known as the axolemma (lemma = sheath). Synapse The synapse is the site of communication between two neurons or between a neuron and an effector cell. Synaptic end bulbs and varicosities contain synaptic vesicles that store a chemical neurotransmitter. Myelination The myelin sheath is a lipid and protein covering. It is produced by the neuroglia. The sheath electrically insulates the axon of a neuron. The sheath increases the speed of nerve impulse conduction. The amount of myelin increases from birth on. Axons without a covering are unmyelinated. Axons with a covering are myelinated. Myelination Continued… Two types of neuroglial cells produce myelination. Schwann cells – located in the PNS. Oligodendrocytes – located in the CNS. Neurolemma (Sheath of Schwann) The neurolemma (sheath of Schwann) is the outer nucleated cytoplasmic layer of the Schwann cell. It encloses the myelin sheath. It is only found around the axons of the PNS. If the axon is injured, the neurolemma forms a regeneration tube that guides and stimulates re-growth of the axon. Nodes of Ranvier The nodes of Ranvier are gaps in the myelin sheath at intervals along the axon. Each Schwann cell wraps one axon segment between two nodes. The electrical impulse jumps from node to node to speed up the propagation Nodes of Ranvier are present in the CNS, but fewer in number. Demyelination Demyelination is the loss or destruction of the myelin sheaths around axons. It occurs as the result of disorders such as multiple sclerosis or Tay-Sachs disease. Radiation and chemotherapy can also damage the myelin sheath. Demyelination can deteriorate the affected nerves. Electrical Signals in Neurons Neurons are electrically excitable and communicate with one another using 2 types of electrical signals. Graded potentials (short distance communication). Action potentials ((long distance communication). The plasma membrane exhibits a membrane potential. The membrane potential is an electrical voltage difference across the membrane. Electrical Signals in Neurons The voltage is termed the resting membrane potential. The flow of charged particles across the membrane is called current. In living cells, the flow of ions constitutes the electrical current. Ion Channels The plasma membrane contains many different kinds of ion channels. The lipid bilayer of the plasma membrane is a good electrical insulator. The main paths for flow of current across the membrane are ion channels. Ion Channels When ion channels are open, they allow specific ions to move across the plasma membrane down their electrochemical gradient. Ions move from greater areas of concentration to lesser areas of concentration. Positively charged cations move towards a negatively charged area and negatively charged anions move towards a positively charged area. As they move, they change the membrane potential. Ion Channel “Gates” Ion channels open and close due to the presence of “gates”. The gate is part of a channel protein that can seal the channel pore shut or move aside to open the pore. Types of Ion Channels Leakage channels Ligand-gated channel Mechanically gated channel Voltage gated channel Leakage Channels Leakage channels – gates randomly alternate between open and closed positions. More potassium ion (K+) leakage channels than sodium (Na+) leakage channels. The potassium ion leakage channels are leakier than the sodium ion leakage channels. Ligand-gated Channel Ligand-gated channels – open and close in response to a specific chemical stimulus. Neurotransmitters, hormones, and certain ions can act as the chemical stimulus that opens or closes these channels. Mechanically Gated Channel Mechanically gated channels – opens or closes in response to mechanical stimulation. Vibration, touch, pressure, or tissue stretching can all distort the channel from its resting position, opening the gate. Voltage-gated Channel Voltage-gated channels – opens in response to a change in membrane potential (voltage). These channels participate in the generation and conduction of action potentials. Gradients Concentration Gradient – A difference in the concentration of a chemical from one place to another. Electrochemical Gradient – The combination of the effects of the concentration gradient and the membrane potential. Transport Across the Membrane Passive Transport – does not require cellular energy. Substances move down their concentration or electrochemical gradients using only their own kinetic energy. Active Transport – requires cellular energy in the form of ATP. 3 Types of Passive Transport Diffusion through the lipid bilayer. Diffusion through membrane channels. Facilitated diffusion. Diffusion Materials diffuse from areas of high concentration to areas of low concentration. The move down their concentration gradient. Equilibrium – molecules are mixed uniformly throughout the solution. Factors Influencing Diffusion Steepness of the concentration gradient. Temperature. Mass of the diffusing substance, Surface area. Diffusion distance. Resting Membrane Potential The resting membrane potential occurs due to a buildup of negative ions in the cytosol along the inside of the membrane and positive ions in the extracellular fluid along the outside of the membrane. The potential energy is measured in millivolts (mV). Resting Membrane Potential In neurons, the resting membrane potential ranges from –40 to –90 mV. Typically –70 mV. The minus sign indicates that the inside of the cell is negative compared to the outside. A cell that exhibits a membrane potential is polarized. The potential exists because of a small buildup of negative ions in the cytosol along the inside of the membrane and positive ions in the extracellular fluid along the membrane. Electrochemical Gradient An electrical difference and a concentration difference across the membrane. Factors Producing the Resting Membrane Potential Unequal distribution of ions in the ECF and cytosol. Inability of most anions to leave the cell. Electrogenic nature of the Na+/K+ ATPases. Unequal distribution of ions in the ECF and cytosol. ECF is rich in Na+ and CL- ions. Cytosol has the cation K+ and the dominant anions are phosphates attached to ATP and amino acids in proteins. The plasma membrane has more K+ leakage channels than Na+ leakage channels. Inability of most anions to leave the cell. The anions are attached to large nondiffusable molecules such as ATP and large proteins. Electrogenic nature of the Na+/K+ ATPases. Membrane permeability to Na+ is very low because there are very few sodium leakage channels. Sodium ions do slowly diffuse into the cell, which would eventually destroy the resting membrane potential. Na+/K+ ATPases pump sodium back out of the cell and bring potassium back in. They pump out 3 Na+ for every 2 K+ they bring in. Graded Potentials A graded potential is a small deviation from the resting membrane potential. It makes the membrane either more polarized (more negative inside) or less polarized (less negative inside). Most graded potentials occur in the dendrites or cell body. Graded Potentials Hyperpolarizing graded potential make the membrane more polarized (inside more negative). Depolarizing graded potential make the membrane less polarized (inside less negative). Graded potentials occur when ligand-gated or mechanically gated channels open or close. Mechanically gated and ligand-gated channels are present in sensory neurons. Ligand-gated channels are present in interneurons and motor neurons. Graded Potentials Graded potentials are graded because they vary in amplitude (size) depending on the strength of the stimulus. The amplitude varies depending upon how many channels are open and how long they are open. The opening and closing of channels produces a flow of current that is localized. Graded Potentials The charge spreads a short distance and dies out (decremental conduction). The charge can become stronger and last longer by adding with other graded potentials (Summation). Types of Graded Potentials Post-synaptic potentials – a graded potential that occurs in the dendrites or cell body of a neuron in response to a neurotransmitter. Receptor potentials and generator potentials – graded potentials that occur in sensory receptors and sensory neurons. Action Potentials An action potential or impulse is a sequence of events that decrease and reverse the membrane potential and eventually restore it to its resting state. Depolarizing phase – the resting membrane potential becomes less negative, reaches zero, and then becomes positive. Repolarizing phase – restores the resting membrane potential to -70 mV. Threshold Threshold – depolarization reaches a certain level (about – 55 mV), voltage gated channels open. A weak stimulus that does not bring the membrane to threshold is called a sub-threshold stimulus. A stimulus that is just strong enough to depolarize a membrane is called a threshold stimulus. Several action potentials will from in response to a suprathreshold stimulus. Action potentials arise according to an all or none principal. Depolarizing Phase A depolarizing graded potential or some other stimulus causes the membrane to reach threshold. Voltage-gated ion channels open rapidly. The inflow of positive Na+ ions changes the membrane potential from –55mv to +30 mV. K+ channels remain largely closed. About 20,000 Na+ enter through the gates. Millions are present in the surrounding fluid. Na+/K+ pumps bail them out. Repolarizing Phase While Na+ channels are opening during depolarization, K+ channels remain largely closed. The closing of Na+ channels and the slow opening of K+ channels allows for repolarization. K+ channels allow outflow of K+ ions. Refractory Period The refractory period is the period of time after an action potential begins during which an excitable cell cannot generate another action potential. Absolute refractory period – a second action potential cannot be initiated, even with a very strong stimulus. Relative refractory period – an action potential can be initiated, but only with a larger than normal stimulus. Propagation of Nerve Impulses Unlike the graded potential, the impulse in the action potential is not detrimental (it does not die out). The impulse must travel from the trigger zone to the axon terminals. This process is known as propagation or conduction. The impulse spreads along the membrane. As Na+ ions flow in, they trigger depolarization which opens Na+ channels in adjacent segments of the membrane. 2 Types of Propagation Continuous Conduction – step by step depolarization and repolarization of each segment of the plasma membrane. Saltatory Conduction – a special mode of action potential propagation along myelinated axons. The action potential “leaps” from one Node of Ranvier to the next. Continuous and Saltatory Conduction Few ion channels are present where there is myelin. Nodes of Ranvier – areas where there is no myelin – contain many ion channels. The impulse “jumps” from node to node. This speeds up the propagation of the impulse. This is a more energy efficient mode of conduction. Neurotoxins & Local Anesthetics Neurotoxins produce poisonous effects upon the nervous system. Local anesthetics are drugs that block pain and other somatic sensations. These both act by blocking the opening of voltage-gated Na+ channels and preventing propagation of nerve impulses. Factors That Affect Speed of Propagation 1. Amount of myelination - Myelinated axons conduct impulses faster than unmyelinated ones. 2. Axon diameter - Larger diameter axons propagate impulses faster than smaller ones. 3. Temperature – Axons propagate action potentials at lower speeds when cooled. Classification of Nerve Fibers A fibers. Largest diameter. Myelinated. Convey touch, pressure, position, thermal sensation. Classification of Nerve Fibers B fibers. Smaller diameter than A fibers. Myelinated. Conduct impulses from the viscera to the brain and spinal cord (part of the ANS). Classification of Nerve Fibers C fibers. Smallest diameter. Unmyelinated. Conduct some sensory impulses and pain impulses from the viscera. Stimulate the heart, smooth muscle, and glands (part of ANS). Encoding Intensity of a Stimulus A light touch feels different than a firmer touch because of the frequency of impulses. The number of sensory neurons recruited (activated) also determines the intensity of the stimulus. Signal Transmission at Synapses Presynaptic neuron – the neuron sending the signal. Postsynaptic neuron – the neuron receiving the message. Axodendritic – from axon to dendrite. Axosomatic – from axon to soma. Axoaxonic – from axon to axon. Types of Synapses Electrical synapse Chemical synapse Electrical Synapses Action potentials conduct directly between adjacent cells through gap junctions. Electrical Synapses Tubular connexons act as tunnels to connect the cytosol of the two cells. Advantages. Faster communication than a chemical synapse. Synchronization – they can synchronize the activity of a group of neurons or muscle fibers. In the heart and visceral smooth muscle this results in coordinated contraction of these muscle fibers. Chemical Synapses The plasma membranes of a presynaptic and postsynaptic neuron in a chemical synapse do not touch one another directly. The space between the neurons is called a synaptic cleft which is filled with interstitial fluid. A neurotransmitter must diffuse through the interstitial fluid in the cleft and bind to receptors on the postsynaptic neuron. The synaptic delay is about 0.5 msec. Removal of Neurotransmitter Diffusion. Enzymatic degradation. Uptake by cells. Into the cells that released them (reuptake). Into neighboring glial cells (uptake). Spatial and Temporal Summation of Postsynaptic Potentials A typical neuron in the CNS receives input from 1000 to 10,000 synapses. Integration of these inputs is known as summation. Spatial and Temporal Summation of Postsynaptic Potentials Spatial summation – summation results from buildup of neurotransmitter released by several presynaptic end bulbs. Temporal summation – summation results from buildup of neurotransmitter released by a single presynaptic end bulb 2 or more times in rapid succession. Neural Circuits Diverging circuit –single presynaptic neuron influences several postsynaptic neurons (i.e. muscle fibers or gland cells). Converging circuit – several presynaptic neruons influence a single post-synaptic neuron (results in a stronger signal). Neural Circuits Reverberating circuit – Branches from later neurons stimulate earlier ones (may last for seconds to hours) (breathing, coordinated muscular activities, waking up, short-term memory). Parallel after-discharge circuit – a presynaptic neuron stimulates a group of neurons that all interact with a common postsynaptic cell (quick stream of impulses) (mathematical calculations). Neural Circuits Neurogenesis in the CNS Birth of new neurons. From undifferentiated stem cells. Epidermal growth factor stimulates growth of neurons and astrocytes. Minimal new growth occurs in the CNS. Inhibition from glial cells. Myelin in the CNS. Damage and Repair in the PNS Axons and dendrites may undergo repair if the cell body is intact, if the Schwann cells are functional, and if scar tissue does not form too quickly. Wallerian degeneration. Schwann cells adjacent to the site of injury grow torwards one another and form a regeneration tube.