Nervous System Anatomy and Physiology (PHR2001M) Past Workshop Materials 2024-2025

Nervous system anatomy and physiology PHR2001 NDH1010 & MB0312 201-PHYS-03 27/09/2024 from 10:0am – 1 pm Dr. Richard Ngomba  Part of the Material for the workshop in week-4 on Neurophysiology star...

Nervous system anatomy and physiology PHR2001 NDH1010 & MB0312 201-PHYS-03 27/09/2024 from 10:0am – 1 pm Dr. Richard Ngomba  Part of the Material for the workshop in week-4 on Neurophysiology starts here Voltage (V) = Current (I) x Resistance (R) Voltage - forces current around circuit (-70mV) Current - flow of ions (K+ +) Resistance How many ion channels present How many are open Capacitance - ability of cell membrane to store charge  Measuring Membrane Potential amplifier microelectrode Reference Resting potential electrode 0 mV cell -80 mV time Intracellular glass microelectrodes Cells are very small so hard to get access to inside First glass microelectrodes Ling and Gerard (1949) The resting membrane potential Requires: 1. Intact cell (semi-permeable) membrane 2. Ionic concentration gradients and ionic permeability's (particularly K+ ions) 3. Over the long term: metabolic processes Julius Bernstein 1880s the ionic theory, the Nernst equation, semi-permeable membrane Ionic concentration gradients intracellular extracellular 120 mM Na+ 12 mM Na+ 125 mM K+ K+ 5 mM 5 mM Cl- Cl- 125 mM 108 mM anions1.2- Ideal plasma membrane: Impermeable to Na+ ions Changing Na+ concentration will not effect resting potential At equilibrium there is a balance between K+ ions moving in and out of the cell this occurs at the resting potential intracellular extracellular concentration gradient 125 mM K+ K+ 5 mM -80 mV electrical gradient concentration electrical gradient gradient Simple model: equal concentrations of ions 0 volts voltmeter Ion selective membrane (only K+, not Cl-) I II Cl- K+ Cl- K+ 0.01 M 0.01 M Cl- K+ KCL KCL Cl- K+ No net movement Simple model: unequal concentrations of ions volts - + Ion selective membrane (only K+, not Cl-) I II Cl- Cl- K+ Cl- K+ K+ 0.10 M 0.01 M KCL KCL K+ Cl- Cl- Cl- K+ K+ K+ concentration gradient  Initial New Equilibrium K+ Cl- K+ K+ Cl- +K+ Cl- K+ K+ + Cl- Cl- Cl- + K+ Cl- K+ K+ + Cl- Cl- K+ K+ K+ + Cl- Cl- K+ K+ + CHEMICAL CHEMICAL ELECTRICAL The balance point, resting potential for ideal membrane or Ek can be calculated Nernst equation Ek = RT log10 [K+]out ZF [K+]in R = gas constant, T = temperature, F =Faraday constant Z = valency RT/ZF ~58 at room temp with monovalent ions When log10 [K+]out = -1 (10 x more K+ in than out) [K+]in Membrane potential = -58 mV  How membrane potential changes with [K+] if membrane is only permeable to K+ ions 20 0 Reduces electrical gradient -20 membrane potential (mV) to balance -40 -60 -80 -100 concentration electrical 1 10 100 gradient gradient log extracellular [K+] Reducing K+ concentration gradient (less difference between [Inside] and [outside]) What contribution do other ions make to Em? inside outside 120 mM Na+ 12 mM Na+ 125 mM K+ K+ 5 mM 5 mM Cl- Cl- 125 mM 108 mM A1.2- Ideally: Membrane is impermeable to Na+ ions Therefore changing concentration will not effect Em ATP-dependent ion Pumps maintain ionic gradients Extracellular 2 K+ 3 Na+ ATP ADP + Pi Intracellular  Quiz 4. Mitochondria are responsible for generating _______ for the cell in the form of _______. a. cytoplasm; ATP b. energy; glucose c. energy; ATP d. cytoplasm; glucose Answer: _________  Transport across cell membranes Diffusion Facilitated diffusion – Ligand gated – Mechanically gated – Voltage gated Active transport Membrane bound protein Example Where Na+ K+ ATPase Voltage- gated Na+ K+ Hillock and un-myelinated axon Mechanically / stretch gated Ca2+ Na+ Ligand gated Cl- Ca 2+ K+ Na+ Dendrite and cell body (ACh, GABA, cAMP, cGMP, ATP) Leaky channels K+ ION Channels  Na K-ATPase http://blausen.com/?Topic=9078 http://blausen.com/?Topic=9358  Potential Change neural communication involved two kinds of potential change / excitation Action potentials- Long distance Graded – short distance Post synaptic End-plate Receptor potentials The Action Potential Major mechanism of neuronal communication Travels down axon to terminals Does not decrement Trigger transmitter release  The Action potential Peak of action potential (overshoot) D undershoot also known as afterhyperpolarisation (AHP) Rising phase of action stimulus measure potential due to Na+ Squid axon membrane potential influx 33 % Na+ 50 % Na+ From Hodgkin and Katz 1949 Na+ channels allow influx of Na+ Voltage gated channels: transmembrane proteins Activated by changes in voltage (depolarisation) Selective for Ionic species eg Na+, K+, Ca2+ etc Na+channels resting potential ~ -70 mV depolarised to –30 mV channels: Closed channels: Open  Why does Na+ move in when channels open: Concentration gradient: inward Inside outside 12 mM 120 mM Electrical gradient: inward Inside -40 mV positive ions Driving force = concentration gradient + electrical gradient What initially depolarises neurones to open the voltage gated Na+ channels? 1. Synaptic transmission: excitatory postsynaptic potentials EPSPs 2. Generator (receptor) potentials (sensory neurones) 3. Inherent properties 4. Experimental EPSPs Na+ channel opening is regenerative Depolarisation Na+ channels open Na+ influx (positive ions moving into the neuron) Action potentials have a threshold  Repolarisation of the action potential 2 ms (a) resting potential ~ -70 mV (b) depolarisation (Na+ moves in via Na+ channels) (c) repolarisation Ion flow during the action potential (membrane potential) (Na+ conductance) (K+ conductance)  Quiz 30. Action potentials are first generated at the axon hillock because this is where _______ are located. a. non-gated K+ channels b. voltage-gated Na+ channels c. transporters d. Na+/K+ pumps Answer: _____________  Quiz 31. During the _______ period, no additional action potentials can be created. a. absolute refractory b. conduction c. integration d. relative refractory Answer: ______________  Refractory period Absolute refractory period – Neurone cannot be re-stimulated – Na channels inactivated Relative refractory period – Greater stimulation required to trigger action potential – K+ still activated Transmission Reflex arc  Quiz Demyelination is most likely to have occurred in those with 1. Auto-immune disease 2. Bacterial Infection 3. Seizures 4. Meningitis 5. Drug abuse