L9 Action Potential.pdf

Membrane Potentials Ionic basis and significance Dr Pallav Sengupta Assistant Professor, Physiology College of Medicine February 21, 2024 www.gmu.ac.ae COLLEGE OF MEDICINE Learning objectives On completion of this unit, the student will be able to: List the causes of membrane potential. Explain the...

Membrane Potentials Ionic basis and significance Dr Pallav Sengupta Assistant Professor, Physiology College of Medicine February 21, 2024 www.gmu.ac.ae COLLEGE OF MEDICINE Learning objectives On completion of this unit, the student will be able to: List the causes of membrane potential. Explain the ionic basis of action potential development. Describe the channel activation and inactivation during action potential development; and Describe the effects of changes in ion concentration on membrane potential. Clinical Case Report: Tachycardia Patient Presentation: DV is a 56-year-old male admitted to the hospital with recurrent ventricular tachycardia. On bedside rounds, the attending says, “Take a look at the medication list and tell me why DV is on amiodarone.” You recall your pharmacology sessions and remind yourself that amiodarone can inactivate the Na+ channels that initially opened to depolarize the membrane. Diagnostic Approach: What is the end result of amiodarone’s actions that prevents DV from having recurrent ventricular tachycardia? RESTING MEMBRANE POTENTIAL (RMP) The potential difference across the membrane of excitable cell Range : at rest -10 to -100 mV Neurons : - 70 mV Skeletal muscle cells : - 90 mV Smooth muscle cells : - 55 mV Retinal cells: -30 mV Ionic distribution DONNAN MEMBRANE POTENTIAL Follows the principle of Gibbs-Donnan Membrane Equilibrium (GDME) ORIGIN OF RMP Cell membrane at rest : negatively charge Primary responsible ions : K+ (Cl- less role) Other ions (Ca, Mg, Cl, bicarbonate etc)  do not contribute directly to RMP of most cells. Inside the cells are large, negatively charged (anionic) proteins  cannot cross the membrane (size is larger)  maintain the negativity charges inside the membrane ORIGIN OF RMP 1) Diffusion of K+ (through the leak channel  membrane 100X more + permeable to K ) 2) Diffusion of Na+ (through the Na +-K+ exchangers 3) Continuous Na+-K+ pump ( 3 Na+ out & 2 K+ in) ACTION POTENTIAL Brief, rapid and transiently large changes of RMP causing the excitable cell intracellularly becomes more positive than the outside of the nerve cell Voltage-gated channels play dominant roles Ranges from +30 to +40 mV VOLTAGE GATED CHANNELS Voltagegated Sodium (Na+) Channel Voltagegated Potassium (K+) Channel TYPES OF VOLTAGE GATED CHANNELS (e.g. calcium channels) ACTION POTENTIAL Voltage Gated SODIUM CHANNEL Equilibrium Potential The Nernst equation gives us information about the forces acting on an ion. If we know the concentration of an ion inside and outside of a cell, we can use the Nernst equation to find the corresponding membrane potential at equilibrium. REFRACTORY PERIOD 1) ABSOLUTE R.P (ARP) The period during which a second action potential cannot be elicited, even with a strong stimulus Because Na+ gated-channels are in the activated state (activation gate open) 2) RELATIVE R.P (RRP) The period during which a stronger than normal stimulus would be able to elicit the second action potential Because the stronger stimulus capable of opening the sodium voltage-gated channel due to activation gate open but the inactivation gate is slower to close. Clinical Case Report: Tachycardia Patient Presentation: DV is a 56-year-old male admitted to the hospital with recurrent ventricular tachycardia. On bedside rounds, the attending says, “Take a look at the medication list and tell me why DV is on amiodarone.” You recall your pharmacology sessions and remind yourself that amiodarone can inactivate the Na+ channels that initially opened to depolarize the membrane. Diagnostic Approach: What is the end result of amiodarone’s actions that prevents DV from having recurrent ventricular tachycardia? Findings on Case Report Thinking back to DV, what is the end result of amiodarone’s actions that prevents him from having recurrent ventricular tachycardia? Discussion You answer, “By inactivating the Na+ channels that initially opened to depolarize the membrane, amiodarone prolongs the absolute refractory period and so prevents a new action potential from being generated. The risk of ventricular tachycardia decreases.” “Succinctly put and absolutely correct,” the attending says. “Now I hope you see how your basic science learning in the classroom can be applicable to clinical medicine.” References 1. Medical Physiology 3rd Edition. Available at https://wwwclinicalkeycom.gmulibrary.com/#!/content/book/3-s2.0-B9781455743773000021?Index Override=GLOBAL 2. Cell Biology 3rd Edition. Aavailable at https://www-clinicalkey-com.gmulibrary.com/#!/content/book/3s2.0-B9780323341264000013?indexOverride=GLOBAL 3. ScholarRx: Action Potential: https://brick-portal.scholarrx.com/annotation/action-potentials 4. PowerPoint on Moodle