Physiology com3-week2
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The document discusses membrane potential and action potentials. It begins by defining action potentials as signals that trigger communication between cells through electrical and chemical signaling. It then discusses: - Excitable cells like neurons, muscle and endocrine cells that are able to generate and conduct action potentials. - The resting membrane potential of -70mV that exists due to ion concentration gradients established by the sodium-potassium pump and selective permeability of the membrane. - How action potentials are initiated when the membrane potential rapidly depolarizes past a threshold due to opening of voltage-gated sodium channels, then repolarizes due to opening of voltage-gated potassium channels.
Physiology com3-week2
- 1. Assoc.Prof.Burcu GEMİCİ BAŞOL Istanbul, 2019 MEDICAL FACULTY PHASE II PHYSIOLOGY LECTURES Membrane Potential and Action Potential YEDITEPE UNIVERSITY
- 2. Action potentials are signals which triggers communication with surrounding cells! WHAT IS ACTION POTENTIAL? Excitable cells! Neurons communicate by a combination of electrical and chemical signaling. Generally, information is integrated and transmitted along the processes of a single neuron electrically and then transmitted to a target cell chemically. The chemical signal then initiates an electrical change in the target cell.
- 3. EXCITABLE CELLS ? NEURON ENDOCRINE CELLS MUSCLE CELLS EXCITABILITY; The ability of generating and conducting action potential. CONDUCTION CONTRACTION SECRETION
- 4. The unequal distribution of ions Na+ is more concentrated outside the cell K+ is more concentrated inside the cell + + + + + + + - - - - - - - + Na+ K+ Electro-Chemical Equilibrium
- 5. Ions and the Resting Potential • Ions are electrically-charged molecules e.g. sodium (Na+ ), potassium (K+ ), chloride (Cl- ). • The resting potential exists because ions are concentrated on different sides of the membrane. • Na+ and Cl- outside the cell. • K+ and organic anions inside the cell. inside outside Na+ Cl- Na+ K+ Cl- K+ Organic anions (-) Na+ Na+ Organic anions (-) Organic anions (-)
- 6. Ions and the Resting Potential/Diffusion Potential
- 7. Na Na K K Ca Ca INTRACELLULAR-EXTRACELLULAR ION CONCENTRATIONS intracellular extracellular 3 Na 2 K ATP Extracellular concentration (mM) Intracellular concentration (mM) THE RESTING MEMBRANE POTENTIAL The resting membrane potential is the electrical potential difference across the plasma membrane of a normal living cell in its unstimulated state. How can we measure the resting membrane potential? It can be measured directly by the insertion of a microelectrode into the cell with a reference electrode in the extracellular fluid.
- 8. EXCITABLE CELL -70 mV : Intracellular area is more negative than (70 mV) extracellular area! (The majority of the ions in intracellular area are negative charged/the majority of the ions in extracellular area are positive charged) THE RESTING MEMBRANE POTENTIAL
- 9. Action potential size, shape, and timing may vary widely between the different cell types, but there are several common characteris- tics, including the existence of a threshold for action potential for- mation, all-or-nothing behavior, overshoots, and afterpotentials. Action Potential
- 10. Action Potential - Phases
- 11. The successive stages of the action potential • Resting stage: – the membrane is “polarized” – -90 mV inside the membrane • Depolarization stage: the potential rapidly rising in the positive direction – Great excess of Na ions = overshoot • Repolarization stage: – Na channels begin to close – Rapid diffusion of K ions to the exterior re-establishes the negative resting potential
- 12. Membrane Potentials Caused by Diffusion
- 13. NERNST EQUATION ConsiNT. EMF (milivolt)= ± 61 log---------------- ConsEXT.
- 14. Nernst Potential •Relation of the diffusion potential to the concentration difference. •The diffusion potential level across a membrane that exactly opposes the net diffusion of a particular ion through the membrane is called the Nernst Potential.
- 15. NERNST EQUATION FOR SODIUM IONS, 15 EMF (milivolt)= - 61. log---------------- 145 = - 61. log 0.10 = - 61 . - 1 = 61 milivolt NERNST EQUATION ConsİNT EMF (milivolt)= ± 61 log---------------- ConsEXT. Extracellular concentration (mM) Intracellular concentration (mM)
- 16. NERNST EQUATION FOR POTASSIUM IONS, 150 EMF (milivolt)= - 61. log -------------- 4 = - 61. log 37,5 = - 61. 1,57 = - 96 milivolt NERNST EQUATION KonsINT EMF (milivolt)= ± 61 log---------------- KonsEXT Extracellular concentration (mM) Intracellular concentration (mM)
- 17. Na+ -K+ pump causes a large concentration gradient • These gradients for each ion are Na (outside): 142 mEq/L Na (inside): 14 mEq/L K (outside): 4 mEq/L K (inside): 140 mEq/L The ratios of the two respective ions: Nainside /Naoutside : 0.1 Kinside /Koutside : 35
- 18. CONTRIBUTORS OF RESTING MEMBRANE POTENTIAL 1. Na-K ATPase 2. K-Na leaking channels (PK >PNa 100X) 3. Contribution of Sodium Ions (61 milivolt) 4. Contribution of Potassium Ions (-94 milivolt ) ~ -70/-90 mV
- 19. Origin of the Normal Resting Potential •Contribution of the potassium diffusion potential •Contribution of Na diffusion through the nerve membrane •Contribution of the Na+ -K+ pump •The net membrane potential with all these factors operating at the same time is about -90 mV.
- 20. Ion Distributions inside/outside a Neuron
- 21. Briefly; • Within a milisecond, the potential difference becomes great enough to block further net K diffusion to the exterior, despite high K ion concentration gradient. • For K ions: in the normal mammalian nerve fiber, the potential difference required is about -94 mV, with the negativity inside the fiber membrane • For Na ions: the potential should be about 61 mV positive inside the fiber in order to block further net diffusion of Na ions to the inside.
- 22. Permeability to several different ions When a membrane is permeable to several different ions, the diffusion potential that develops depends on three factors: 1) Polarity of the electrical charge of each ion 2) Permeability of the membrane 3) Concentrations of the respective ions on the inside and outside of the membrane Goldman equation
- 23. Membrane potential is not a potential. It is a difference of two potentials so it is a Voltage in fact. Membrane Potential “The term “membrane potential” refers to the voltage difference that exists across the plasma membrane. By convention, the ECF is considered to be at zero volts, or electrical “ground.”
- 24. Number of ions needed for membrane potential ? • An incredibly small number of ions needs to be transferred through the membrane to establish the normal “resting potential” of a -90 mV inside the nerve fiber. • i.e. only about 1/3,000,000 to 1/100,000,000 of the total positive charges inside the fiber needs to be transferred. • An equally small number of positive ions moving from outside to inside the fiber can reverse the potential from -90 mV to as much as +35 mV within 1/10,000 of a second.
- 25. Resting Membrane Potential of Nerves • RMP of large nerve fibers is about -90 mV • i.e. the potential inside the fiber is 90 mV more negative than the extracellular fluid on outside of the fiber. • Na+ -K+ Pump: This powerful system continually pumps Na ions to the outside and K ions to the inside of the cell. • The membrane is about 100 times more permeable to K ions than Na.
- 26. Nerve Action Potential • Nerve signals are transmitted by action potentials. • They are rapid changes in the membrane potential that spread rapidly along the nerve fiber membrane
- 27. Action Potential >>>>>>>>>>>> Ion Conductivity Voltage gated channels are responsible for generating and conducting action potential.
- 28. A, The nongated channel remains open, permitting the free movement of ions across the membrane. B, The ligand-gated channel remains closed (or open) until the binding of a neurotransmitter. C, The voltage-gated channel remains closed until there is a change in membrane potential. The three types of ion channels
- 29. GENERAL STRUCTURE OF VOLTAGE GATED SODIUM CHANNELS 1.Pore for ion transition 2. Sensor which senses voltage changes 3. Gate, regulates ion transition 4. Selective filter, decides which ion will pass or not. 1 2 3 4
- 30. TYPES OF VOLTAGE GATED ION CHANNELS VOLTAGE GATED SODIUM (Na) CHANNEL VOLTAGE GATED POTASSIUM (K) CHANNEL VOLTAGE GATED CALSIUM (Ca) CHANNEL
- 31. Voltage Gated Na and K Channels • The necessary actor in causing both depolarization and repolarization of the nerve membrane during AP is the voltage-gated Na channel • Voltage-gated K channel is also important • These two voltage-gated channels are in addition to the Na+ -K+ pump and K+ -Na leak channels
- 32. Voltage Gated Na and K Channels
- 33. Voltage Gated Na Channel: Activation and Inactivation • A rise in memmbrane potential (MP) in positive direction • A voltage between -70 and -50 mV causes a sudden conformational change in the activation gate • The same increase in voltage that opens the activation gate also closes the inactivation gate. • So, Na ions no longer can pour to the inside of membrane • Inactivation gate will not re-open until the MP returns to or near the original resting MP level.
- 34. Voltage Gated K Channel and Its Activation • During the resting state, K gate is closed • When MP rises from -90 mV toward zero, this voltage change causes a conformational openning of the gate and allows increased K diffusion outward through the channel. • K channel opens just at the same time that Na channel is beginning to close because of inactivation
- 35. Summary of the Events That Cause Action Potential • Influx of Na ions (5000 fold increase in Na conductance • Na channels begin to close and K channels to open • Rapid loss of K ions to the exterior • Returning to the baseline level
- 36. The states of voltage-gated sodium and potassium channels correlated with the course of the action potential. A, At the resting membrane potential, both channels are in a closed, resting state. B, During the depolarizing phase of the action potential the voltage-gated sodium channels are activated (open), but the potassium channels open more slowly and, therefore, have not yet responded to the depolarization. C, During the repolarizing phase, sodium channels become inactivated, while the potassium channels become activated (open). D, During the after hyperpolarization, the sodium channels are both closed and inactivated, and the potassium channels remain in their active state. Eventually, the potassium channels close and the sodium channel inactivation is removed, so that both channels are in their resting state and the membrane potential returns to resting membrane potential. Note that the voltage-gated potassium channel does not have an inactivated state
- 37. Initiation of the Action Potential • A positive feedback vicious cycle opens the Na channels • Threshold for initiation of the action potential • A sudden rise in membrane potential of 15 to 30 mV is required • -65 mV is the threshold for stimulation
- 38. Propagation of the Action Potential • Action potential occurs at one spot on the membrane • It then excites adjacent portions of the membrane, resulting in propagation of the AP along the membrane. • Direction of propagation: in all directions from the stimulus, until the entire membrane is depolarized. • All-or-Nothing Principle: Sometimes AP reaches a point where it does not generate sufficient voltage to stimulate the next area of the membrane. • When this happens, the spread of polarization stops. 1
- 39. Plateau in Some Action Potentials • In some cases, the excited membrane does not immediately repolarize after depolarization. • Instead, the potential remains on a plateau near the peak of the spike potential for some miliseconds, then depolarization begins. • This happens in the cardiac muscle fibers (0.2 to 0.3 sec delay) • Two types of channels in the heart muscle: • Voltage-gated Na channels • Voltage-activated Ca-Na channels • Second factor: voltage-gated K channels are slower than usual to open
- 40. Special characteristics of signal transmission in nerve trunks • Myelinated and unmyelinated nerve fibers • Schwann cell and sphingomyelin • Node of Ranvier
- 41. “Saltatory” conduction in myelinated fibers from node to node • No ions can flow through the thick myelin sheats • They can flow easily through the nodes of Ranvier • Thus, action potential (AP) can only occur at the nodes • The AP is conducted from node to node (which is called saltatory conduction) • Electrical current flows through the surrounding extracellular fluid as well as through the axoplasm • This mechanism • Increases the velocity • Conserves energy Node of Ranvier and Action Potential Node of Ranvier Myelin sheath
- 42. “Saltatory” conduction in myelinated fibers from node to node * Velocity of conduction in nerve fibers varies from 0.25 m/sn (unmyelinated) to 100 m/sn (myelinated)
- 43. Excitation (process of eliciting action potential) What causes the action potential? Any factor that causes Na ions to begin to diffuse inward the membrane in sufficient numbers can set off automatic regenerative openning of Na channels. 1) Mechanical disturbance of the membrane (nerve endings in the skin) 2) Chemical effects on the membrane 3) Electrical current to transmit signals between muscle cells in the heart and intestine.
- 44. Refractory Period • A new potential cannot occur in an excitable fiber as long as the membrane is still depolarized from the previous AP. • The period during which a second AP cannot be elicited (even with a strong stimulus) is called absolute refractory period.
- 45. Recording Membrane and Action Potentials
- 46. Excitation of a Nerve Fiber by Negatively Charged Metal Electrode • Application of electricity to the nerve or muscle surface through two small electrodes (one negative and one positively charged) • The excitable membrane becomes stimulated at the negative electrode • The negative current from the electrode decreases the voltage on the outside of membrane to a negative value nearer the negative potential inside the fiber.
- 47. EMG Lab