Muscle Physiology L01 - Summer 24 PDF

MUSCLE PHYSIOLOGY 1. Membrane potential and action potential Andre Azevedo, DVM, MSc Visiting Professor of Veterinary Physiology [email protected] Learning objectives for this lecture Describe how resting membrane potentials are generated Describe the phases of an action potential a...

MUSCLE PHYSIOLOGY 1. Membrane potential and action potential Andre Azevedo, DVM, MSc Visiting Professor of Veterinary Physiology [email protected] Learning objectives for this lecture Describe how resting membrane potentials are generated Describe the phases of an action potential and how they occur Diffusion potential Concentration gradient + Uncharged molecules: what is the driving force? Charged molecules: what are the driving forces? [Na+] electrical charges [Na+] [Na+] two solutions separated by a theoretical membrane that is permeable to Na + but not to Cl− Concentration gradient [Na+] [Cl-] [Na+] [Cl-] [Na+] [Cl ] - + + + [Na+] [Cl-] A diffusion potential is the potential difference generated across a membrane when a charged solute (an ion) diffuses down its concentration gradient. Equilibrium potential [Na+] [Cl-] [Na+] [Cl-] [Na+] [Cl ] - + + + [Na+] [Cl-] The diffusion potential depends on the concentration gradient and permeability of the membrane If the membrane is not permeable to that ion, no diffusion potential will be generated If there is no difference in concentration, no diffusion potential will be generated Diffusion potentials are created by the movement of only a few ions (infinitesimal amount) they do not cause measurable changes in the concentration of ions in bulk solution However, this infinitesimal amount is enough to bring about a rather large change in electrical potential (diffusion potential). The diffusion potential that exactly balances the tendency of an ion to diffuse down its concentration gradient is the ion’s equilibrium potential or Nernst potential (calculated by the Nernst equation) Based on the electrical charge of the ion and the concentration inside and outside the membrane, the equilibrium potential of each ion can be calculated Typical values (FYI only): ENa+ = +65 mV ECa2+ = +120 mV EK+ = –85 mV ECl– = –90 mV Membrane potential MEMBRANE POTENTIAL is the difference in electric potential between the interior and exterior of a biological cell Membrane potential exists across the membrane of virtually all cells The membrane potential depends on the equilibrium potential of the different ions and the relative permeability of each ion The potential across the surface membrane of most animal cells generally does not vary with time In contrast, neurons and muscle cells (the principal types of electrically active cells) undergo controlled changes in their membrane potential When the membrane potential of a cell goes for a long period of time without changing significantly, it is referred to as a RESTING POTENTIAL. the membrane potential of non-excitable cells the membrane potential of excitable cells in the absence of excitation The resting potential of nerve fibers when not transmitting nerve signals is around -70 millivolts (-40 to -90 mV) The potential inside the fiber is 70 millivolts more negative than the outside Resting potential on nerve cells Factors that mainly determine the resting potential include: 1. DIFFUSION OF POTASSIUM THROUGH THE NERVE CELL MEMBRANE 2. DIFFUSION OF SODIUM THROUGH THE NERVE CELL MEMBRANE 3. THE Na-K PUMP Na-K-ATPase Resting potential on nerve cells 1. DIFFUSION OF POTASSIUM THROUGH THE NERVE CELL MEMBRANE Potassium leak channels allow K ions to diffuse out of the cell The selectivity of the channel is 100x higher for K than for Na ions Protein anions remain inside the cell K also moves into the cell attracted to negative charges Resting potential on nerve cells 2. DIFFUSION OF SODIUM THROUGH THE NERVE CELL MEMBRANE Sodium leak channels allow Na ions to diffuse into the cell The membrane is far less permeable to Na than to K ions Potassium diffusion is the most important contributor to resting potential Resting potential on nerve cells 3. CONTRIBUTION OF THE Na-K PUMP Continually transports Na out and K in 2 K+ ions bind on the outside of the pump, and 3 Na+ ions bind on the inside ATPase function of the protein becomes activated after binding Additionally contributes to the negative resting potential Recall that it is also an important way to control the volume Resting potential on nerve cells Resting potential video https://www.youtube.com/watch?v=YP_P6bYvEjE Action potential Neurons and muscle cells (excitable cells) can generate, transmit and receive electric signals by changing the membrane potential Changes in ion concentrations and permeabilities play crucial roles in the dynamic changes of the membrane potential Due to: changes in activity of membrane pumps opening and closing of ion channels Nerve signals are transmitted by ACTION POTENTIALS (AP) Rapid changes in the membrane potential that spread rapidly along the nerve fiber membrane Each action potential begins with a sudden change from the normal resting negative membrane potential to a positive potential It ends with an almost equally rapid change back to the negative potential The AP moves along the nerve fiber until it comes to the fiber’s end Action potential The action potential can be divided in five stages: 1. Resting stage 2. Threshold 3. Depolarization 4. Repolarization 5. Hyperpolarization (relative refractory period) Action potential (1) RESTING STAGE Is the resting membrane potential Moment before AP begins Membrane is said to be “polarized” because of the negative MP (-70 mV) Action potential (2) THRESHOLD A threshold for the initiation of the action potential needs to be achieved Rise in membrane potential of 15-30 mV THRESHOLD POTENTIAL or THRESHOLD VOLTAGE The minimal membrane potential (voltage) to trigger an action potential (-55 mV) After mechanical, chemical, or electrical stimuli Action potential (3) DEPOLARIZATION At this time, the membrane suddenly becomes permeable to sodium ions Massive movement of positively charged Na ions to the interior of the axon Occurs through VOLTAGE-GATED SODIUM CHANNELS They are activated when the membrane potential starts to change It is a positive feedback cycle (the initial opening of a few facilitate the opening of the remaining) Membrane potential rising in the positive direction is called DEPOLARIZATION In the late part of depolarization, VOLTAGE-GATED POTASSIUM CHANNELS start to open, slowing down the depolarization (think as “ depolarization brakes”) Action potential (4) REPOLARIZATION After the membrane becomes highly permeable to sodium ions, Na channels begin to close VOLTAGE-GATED POTASSIUM CHANNELS still opened cause a rapid diffusion of K ions out of the cell lowering the membrane potential The re-establishment of the normal negative resting potential is called REPOLARIZATION Action potential (5) HYPERPOLARIZATION Neurons enter a state of hyperpolarization immediately after the generation of an action potential – membrane more negative than normal Combination of no more positive ions (Na) flowing into and positive ions (K) still leaving the cell ABSOLUTE REFRACTORY PERIOD: Corresponds to nearly the entire duration of the AP The time needed for the voltage-gated sodium channels to revert from the inactivated state to the resting closed state The only condition that will allow them to reopen is the returning of the original resting potential AP initiation is completely blocked RELATIVE REFRACTORY PERIOD: Corresponds to the hyperpolarization state The time when voltage-gated sodium channels are closed, but not inactive anymore AP is harder to achieve because of the “extra-negative” membrane potential, but not completed blocked. If a strong stimulus reaches the threshold, AP is generated Propagation of the action potential An AP elicited at any one point on an excitable membrane usually excites adjacent portions of the membrane Travels in all directions away from the stimulus The refractory period in the already depolarized area forces a direction of propagation along the membrane of the axon Until the entire membrane has become depolarized Action potential video https://www.youtube.com/watch?v=fHRC8SlLcH0 Questions?