2024 Nerve and Muscle Slides PDF

PHS 205 Nerve and Muscle Physiology COURSE UNIT-2 Lecturer: Olusoji Adeola Adalumo Department of Physiology, SBMS, FUTA  Outline  A brief introduction to Physiology  The Neuron or Nerve Cell  Orthograde and Retrograde Neuronal Transp...

PHS 205 Nerve and Muscle Physiology COURSE UNIT-2 Lecturer: Olusoji Adeola Adalumo Department of Physiology, SBMS, FUTA  Outline  A brief introduction to Physiology  The Neuron or Nerve Cell  Orthograde and Retrograde Neuronal Transport  Resting Membrane Potential (RMP)  Action Potential - Depolarization, Repolarization and Hyperpolarization, Refractory Periods, Chronaxie, Rheobase  Outline contd.  Graded Potentials  All or None Law of Impulse Conduction and Transmission  Saltatory Conduction  Synaptic and Junctional Transmission, EPSPs and IPSPs  Nerve-Muscle Relation  Neuromuscular Transmission  A brief introduction to Physiology  Outline  A brief introduction to Physiology  Outline  A brief introduction to Physiology Historical Background: The Discovery of the Nerve Impulse  Du Bois-Reymond (1818-1896). The Physician who first noticed a negative variation during stimulation of a nerve (Action Potential).  Julius Bernstein (1838-1917). His membrane theory explains activities in neurons as a phenomenon caused by differences in ion-concentrations inside vs outside the cell.  The Neuron or Nerve Cell  An excitable tissue.  The structural and functional unit of the nervous system.  The human CNS contains about (100 billion) neurons.  Contains 10–50 times this number of glia cells  The Neuron or Nerve Cell  The structural and functional unit of the nervous system.  Neurons integrate and transmit electrical impulses (action potentials, receptor potentials, and synaptic potentials).  The Neuron or Nerve Cell  It is similar to other cells in the body  Structurally different by having branches or processes called axons and dendrites  No centrosome, hence no cell division  The Neuron or Nerve Cell Motor neuron with a myelinated axon  The Neuron or Nerve Cell  Classification 1. Unipolar neurons 2. Bipolar neurons 3. Multipolar neurons  The cell body maintains the functional and anatomic integrity of the axon; If the axon is lesioned, the part distal to the cut degenerates (Wallerian degeneration). A Nerve cell or Neuron has potential for remodeling in response to injury during early development than in the adult brain, a characteristic known as plasticity. Lesion to axons can be repaired, and significant function restored, if (1) the damage occurs outside the CNS and (2) does not affect the neuron’s cell body. Restoration of function following a peripheral nerve injury is slow Axon regrowth proceeds at a rate of only 1 mm per day.  Spinal injuries typically crush rather than cut the tissue, leaving the axons intact. In this case, apoptosis of the oligodendrocytes result in the loss of the myelin coat and the axons cannot transmit information effectively. Severed axons within the CNS may grow small new extensions but no significant regeneration of the axon occurs across the damaged site, and there are no well- documented reports of significant return of function.  Orthograde transport moves from the cell body toward the axon terminals. It has both fast and slow components; fast axonal transport occurs at about 400 mm/day, and slow axonal transport occurs at 0.5 to 10 mm/day. Orthograde transport occurs along microtubules that run along the length of the axon and requires two molecular motors, dynein and kinesin (Figure on next slide).  Retrograde transport, which is in the opposite direction (from the nerve ending to the cell body), occurs along microtubules at about 200 mm/day. Synaptic vesicles recycle in the membrane, but some used vesicles are carried back to the cell body and deposited in lysosomes. Some materials taken up at the ending by endocytosis, including nerve growth factor (NGF) and various viruses, are also transported back to the cell body.  References Thank You for your Attention!  Diffusion and Equilibrium Potentials  Diffusion Potential – the potential difference generated across a permeable membrane to an ion due to a concentration difference of the same ion.  Equilibrium Potential - The potential difference that would stop the tendency for diffusion down a concentration difference. Generation of Na+ Diffusion Potential Across a Na+ Selective Membrane  At electrochemical equilibrium - chemical and electrical driving forces acting on an ion are equal and opposite; - no net diffusion of the ion occurs. Calculating Equilibrium Potentials (Nernst Equation) At what potential would an ion be at electrochemical equilibrium?  Calculating Equilibrium Potentials (Nernst Equation) The Resting Membrane Potential (RMP)  The measured potential difference across the cell membrane in millivolts (mV).  Expressed as the intracellular potential relative to the extracellular potential.  Thus, a resting membrane potential of -70 mV means 70 mV, cell negative. The Resting Membrane Potential (RMP) The Resting Membrane Potential (RMP)  The RMP is established by diffusion potentials resulting from concentration differences of permeant ions.  At rest, the nerve membrane is far more permeable to K+ than to Na+.  The RMP of a nerve is -70 mV, which is close to the calculated K+ equilibrium potential of -85 mV, not Na+ equilibrium potential of +65 mV. The Resting Membrane Potential (RMP) First, the action of the Na+/K+-ATPase pump sets up the concentration gradients for Na+ and K+ Greater flux of K+ out of the cell than Na+ into the cell (Figure 6–13b). This is because in a resting membrane there are a greater number of open K+ channels than there are Na+ channels. Because there is greater net efflux than influx of positive ions during this step, a significant negative membrane potential develops, with the value approaching that of the K+ equilibrium potential.  In the steady-state, the flux of ions across the membrane reaches a dynamic balance (Figure 6– 13c). Because the membrane potential is not equal to the equilibrium potential for either ion, there is a small but steady leak of Na+ into the cell and K+ out of the cell. References  Thank You for your Attention! ACTION POTENTIAL Action potential is an essential attribute (property) of all excitable cells (nerve, muscle) consisting of a rapid depolarization, or upstroke, followed by repolarisation of the membrane potential. Action potentials have stereotypical size and shape, are propagating, and are all-or-none.  ACTION POTENTIAL Action potentials are generally very rapid (as brief as 1–4 milliseconds) and may repeat at frequencies of several hundred per second. An action potential is a large change in membrane potential and is an “all or none” response. ACTION POTENTIAL  ACTION POTENTIAL contd. Depolarization is the potential moving from RMP to less negative values. Repolarization is the potential moving back to the RMP. Hyperpolarization is the potential moving away from the RMP in a more negative direction. Clinical Effects of Action Potential Inhibition  Without action potentials, graded signals generated in the periphery—in response to injury, for example—cannot reach the brain and give rise to the sensation of pain. Clinical Effects of Action Potential Inhibition  The generation of action potentials is prevented by local anesthetics such as procaine (Novocaine®) and lidocaine (Xylocaine®) because these drugs block voltage-gated Na+ channels. ACTION POTENTIAL: REFRACTORY PERIODS There are 2 types : i) Absolute refractory and; ii) Relative refractory. The Absolute Refractory Period (ARP): During action potential, a second stimulus, no matter how strong, will not produce a second action potential. Occurs when the voltage-gated Na+ channels are either already open or have proceeded to the inactivated state during the first action potential.  REFRACTORY PERIODS  Relative refractory period, an interval during which a second action potential can be produced.  Provided the stimulus strength is considerably greater than usual.  The refractory periods limit the number of action potentials an excitable membrane can produce in a given period of time.  Most neurons respond at frequencies of up to 100 action potentials per second, and some may produce much higher frequencies for brief periods.  The refractory periods also are the key in determining the direction of action potential propagation.  Refractory periods contribute to the separation of these action potentials so that individual electrical signals pass down the axon.  PROPAGATION OF ACTION POTENTIAL Propagation via saltatory conduction is faster than propagation in non-myelinated fibers of the same axon diameter. Moreover, because ions cross the membrane only at the nodes of Ranvier, the membrane pumps need to restore fewer ions. Myelinated axons are metabolically more efficient than un-myelinated ones. Myelin adds speed, reduces metabolic cost, and saves room in the nervous system because the axons can be thinner. Conduction velocity is increased by: a. ↑ fiber size. Increasing the diameter of a nerve fiber results in decreased internal resistance; thus, conduction velocity down the nerve is faster. b. Myelination. Myelin acts as an insulator around nerve axons and increases conduction velocity.  SUMMATION  When two or more subliminal stimuli are applied within a short interval (0.5 millisecond) a response is produced.  The subliminal stimuli are summed up together to become strong enough to produce the response. ADAPTATION  While stimulating a nerve fiber continuously, the excitability of the nerve fiber is greater in the beginning.  Later the response decreases slowly and finally the nerve fiber does not show any response at all.  References Thank You for your Attention!  RHEOBASE  The minimum strength (voltage) of stimulus, that can excite the tissue.  The voltage below this cannot excite the tissue, no matter the duration. CHRONAXIE  The minimum time (m sec) required for a stimulus with double the rheobasic strength (voltage) to excite the tissue.  The longer the chronaxie, the lesser is the excitability of the tissue.  STRENGTH-DURATION CURVE GRADED POTENTIAL  small local change in the membrane potential.  develops in receptors, synapses or neuro- muscular junction when stimulated. SYNAPTIC & JUNCTIONAL TRANSMISSION  Synapse is the junction between two neurons, or neuron and muscle.  Excitatory Postsynaptic Potentials (EPSPs).  Depolarizes postsynaptic cell, bringing it closer to threshold and closer to firing an action potential. SYNAPTIC & JUNCTIONAL TRANSMISSION  Inhibitory Postsynaptic Potentials (IPSPs).  Hyperpolarizes postsynaptic cell, moving it away from threshold and farther from firing an action potential. NEUROMUSCULAR TRANSMISSION The steps: 1. AP arrives at the nerve terminal. 2. Voltage-gated Ca2+ channels open. 3. Ca2+ levels rise and cause vesicles to fuse with the synaptic membrane, releasing neurotransmitter into the synaptic cleft. NEUROMUSCULAR TRANSMISSION The steps: 4. Transmitter binds to a receptor on the postsynaptic membrane 5. Transmission is terminated. TERMINATION OF NEUROTRANSMISSION Mechanisms: 1. Degradation : The synaptic cleft usually contains enzymes that degrade the neurotransmitter (e.g. acetylcholinesterase. 2. Recycling : Transmitter is taken up by the neuron or glia and recycled. 3. Diffusion : Transmitter diffuses out of the cleft. NEUROMUSCULAR TRANSMISSION TERMINATION OF NEUROTRANSMISSION Toxins:  Clostridium botulinum inhibits the release of acetylcholine &  Clostridium tetani are related microbes that kill their hosts by interfering with neuromuscular transmission. TERMINATION OF NEUROTRANSMISSION Tetanus:  C. tetani travels to the CNS and prevents glycine and GABA release, thereby disrupting inhibitory pathways that normally limit muscle contractions.  Patients may suffer painful muscle spasms and tetanic contractions as a result. OTHER AGENTS AFFECTING NEUROTRANSMISSION NEUROTRANSMITERS  ACh.  Norepinephrine, Epinephrine & Dopamine  Serotonin  Histamine  Glutamate  GABA Inhibitory  Glycine  Nitric Oxide Synthetic Pathway for Dopamine Norepinephrine & Epinephrine References  Thank You for your Attention!