Biophysics - Physiology Lecture 5 PDF

# Action Potential ## Prof. Sahar El Agaty | Professor of Physiology ## Biophysics - Physiology Lecture 5 ### Powered by Arizona State University ### gu.edu.eg # Intended Learning Outcomes - Discuss causes of resting membrane potential. - Demonstrate ionic basis of action potential. - Differentiat...

# Action Potential ## Prof. Sahar El Agaty | Professor of Physiology ## Biophysics - Physiology Lecture 5 ### Powered by Arizona State University ### gu.edu.eg # Intended Learning Outcomes - Discuss causes of resting membrane potential. - Demonstrate ionic basis of action potential. - Differentiate between action potential and local potential. # Membrane potential - The term **membrane potential** refers to the difference in the relative number of cations and anion in the ICF and ECF. - There are excess of positive charges outside the cell and negative charges inside the cell at rest. # Membrane Potential - If the amount of positive charges and negative charges are equal, then there is no potential in the membrane. - If there are more positive charges on one side of the membrane than the other, then the membrane has potential. - Separated charges are responsible for potential - Separated charges form a layer along the plasma membrane. # Membrane Potential - The magnitude of the potential depends on the number of opposite charges separated. - The greater the number of charges separated, the larger the potential. # Membrane potential and excitable tissues - All cells have resting membrane potential produced by the accumulation of positive charges outside the cell membrane and negative charges inside. - Nerve and muscles are **excitable tissues** that can respond to a stimulus by producing rapid, transient changes in their membrane potential. - These brief fluctuations in potential act as electrical signals and is called **action potential**. - Electric events in excitable tissues are rapid (measured in milliseconds) and small (measured in millivolt). - These electric changes can be measured by 2 electrodes of galvanometer; one is outside the cell membrane and the other is inside: **(monophasic action potential)**. - If the 2 electrodes are applied on the outside of the cell membrane a **biphasic action potential** is recorded. # Properties of excitable tissues - They have a high transmembrane potential. - Their cell membranes contain ion channels that open and close their gates with changes in membrane potential **(voltage gated channels e.g., Na+, K+, and Ca2+ channels)** Also, excitable cells have ligand gated channels. - The passage of these ions in and out of the cell produces the electric response upon stimulation of excitable tissues. # Resting membrane potential (RMP) ## Definition: - It is the voltage difference across the cell membrane of excitable tissues (nerve and muscles) during resting state. - Under resting condition, the inside of the membrane is more negative than outside. - The resting membrane potential of neurons is usually about –70 mV. - The ions directly responsible for generating the resting membrane potential are Na+ and K+. The presence of large, negatively charged (anionic) intracellular proteins, is also important. - Other ions (calcium, magnesium, and chloride) do not contribute to the resting electrical properties of the plasma membrane in most cells. # Causes of RMP - **Passive forces (93%):** It is produced by the selective permeability of the cell membrane. - **A) Permeability to K+ and Na+ :** - Because of high intracellular levels of K+, the concentration gradient of K+ ions favor the passive movement of K+ out of the cell (efflux). This K+ efflux occurs via K+ leaky channels. - Also, the high extracellular level of Na+ favors the passive movement of Na+ into the cell (influx) by the concentration gradient. This Na+ influx occurs via Na+ leaky channels. - **B) Permeability to intracellular proteins:** The membrane is impermeable to intracellular, negatively charged protein which is trapped inside the cell. This adds to the negativity of the interior of the cell. - **Active force (7%):** - It is produced by Na+-K+ pump. - It pumps the leaked Na+ to outside of the cell and the leaked K+ to the inside of the cell. - It transfer 3 Na+ ions out of the cell and 2K+ jons to inside of the cell ( its coupling ratio is 3/2). Therefore, it keeps the negativity of the RMP as it transfer more positive charges out of the cell. # Membrane potential - **Polarized state (RMP):** It is the membrane potential at rest (e.g., -70 mv in nerve). The interior is negative relative to the exterior - **Depolarized state:** It is a decrease in membrane potential negativity (e.g., -60, -50, -40 mv). The interior is less negative than the resting potential or even become positive relative to the exterior (e.g., +10, +20, +30) - **Hyperpolarized state:** It is an increase in membrane potential negativity (e.g., -90, -100 mv). The interior is more negative than the resting potential. # Student Activity ## True and false - Resting membrane potential in excitable tissues is usually negative. **T** - Maintenance of RMP is mainly active process. **F** (Passive) - Proteins are trapped intracellularly and thus create negativity inside the cell. **T** # Neuron: Basic Working unit of the nervous system - Neuron or nerve cell is the basic working unit of the nervous system. - They are electrically excitable cells that receive, conduct and transmit information in a form of action potential (electric signal). ## Structure of neuron: - **Cell body (soma)** contains cytoplasm, nucleus, and organelles - **Dendrites** extend outward from the cell body. They receive signals from other nerve cells and transmit them toward the cell body. - **Axon** is a long process that arise from a thickened area in the cell body called axon hillock. It form branches at its end called axon terminal which form terminal buttons (synaptic knobs) that contain synaptic vesicles which store neurotransmitter. It is called nerve fiber. ## Myelin sheath: - Some axons are covered by myelin sheath. It is a protein-lipid complex that is wrapped around the axon. It is formed by **Schwan cells**. There is gaps between Schwan cells called nodes of Ranvier. ## Function of myelin sheath: - Protects the nerve fiber - Electrically insulates the nerve fiber - Increases the speed of conduction of nerve impulse. ## Function of neuron - Receives information. - Conducts information. - Transmits information to another neuron, muscle, or gland. # Motor signals are conducted from the central nervous system by neurons in a form of action potential leading to movement of our muscles - Primary motor cortex - Internal capsule - Upper motor neuron - Medulla pyramid - Corticospinal tract - Lower motor neuron ## Muscle contraction is initiated by action potential. # Sensory signals are conducted to the central nervous system by neurons in a form of action potential - Primary somatosensory cortex - Third-order neuron - Thalamus - Second-order neuron - Medulla oblongata - Spinal cord - Lissauer's tract - Nociceptors or thermoreceptors - First-order neuron (afferent) # Action potential of a neuron ## Stimulus - Stimulus is a change in the external or internal environment that is detected by receptor. - It may be electrical, thermal, mechanical, or chemical. - In experimental studying of nerve, electric stimulus is used as its intensity and duration can be precisely controlled. - The minimal intensity of stimulating current needed to produce an action potential is called the **threshold stimulus**. ## N.B.** Receptors in our body can change the chemical, mechanical and thermal stimuli into potential change (local potential) that if large enough it will be conducted along a nerve fiber as an action potential. For example: cold sensation is a thermal stimulus, and touch sensation is a mechanical stimulus. # Action potential phases and ionic basis ## Definition - It is a transient reversal of membrane polarity produced by stimulation of excitable tissues by a **threshold stimulus** that reduce the negativity of membrane potential to threshold value. - It can be recorded by galvanometer and amplifier via 2 microelectrodes, one inside the nerve and the other is placed on the outer surface of the nerve. The recorded potential is called **monophasic action potential**. - It is produced mainly by change in behavior of Na+ and K+ channels, leading to change in conductance of these ions. ## Phases of action potential: - **Latent period:** - It is the time interval from application of the stimulus to the start of depolarization. - It is the time required to conduct the stimulus to the recording electrode. - **Depolarization phase:** - It is produced by Na⁺ influx which reverse the membrane polarity. - **Steps:** - **Step 1:** Arrival of a depolarizing stimulus. Opening of some voltage gated Na+ channels and Na influx by concentration gradient. - **Step 2:** The membrane potential is brought to the **threshold potential** (firing level) (-55mv) [depolarization of 15 mv]. - **Step 3:** The entry of Na + causes the opening of more voltage-gated Na + channels and further depolarization, setting up a positive feedback loop. As Na+ influx proceeds, a rapid upstroke of the membrane potential (overshooting the zero level) is reached. - **Step 4:** The potential reaches +35 mv (reversal of polarity). The interior of the nerve becomes positive relative to the exterior which limits Na+ influx. - **The amplitude of action potential is 105 mv.** - **Repolarization phase:** - **Step 5:** Repolarization is produced by Closure of voltage gated Na+ channels and opening of voltage gated K+ channels and K+ efflux by concentration gradient → fall of membrane potential toward the resting state. - The opening of voltage-gated K + channels is slower and more prolonged than the opening of the Na + channels. - When repolarization is 70% its rate is decreased which is called **after depolarization**. - **Step 6:** It is produced by slow return of the K + channels to the closed state which leads to the **afterhyperpolarization** ( -90 mv). - **Step 7:** The membrane potential returns to the resting state (RMP). The RMP is restored when K+ channels completely closed. Any excess Na+ inside or less K+ inside the cell will be adjusted by Na+-K+ pump. ## Voltage dependent Na+ and K+ channels in action potential - **Voltage dependent Na+ Channel:** - Has activation gate (m-gate, in extracellular side of the channel), and inactivation gate (h-gate, in the intracellular side of the channel). - During rest: the inactivation gate is opened, and the activation gate is closed. - During depolarization: there is immediate opening of the m-gate and slow closure of h-gate. - During repolarization: there is recovery to resting state to be ready for the next response. - **Functional stages of the channel:** - Resting stage (reactive) h-gate is opened and m-gate is closed. - Active stage: h and m gates are opened. - Inactive stage: h gate is closed. - **Voltage dependent K+ channel:** - It has one activation gate (n-gate). - It opens and closes very slowly. - It opens during repolarization and closes when the RMP is achieved. ## Feedback control of voltage-gated ion channels - **A) Na+ channels exert positive feedback.** - **B) K+ channels exert negative feedback.** # Excitability change and refractory periods during action potential ## Excitability: - Is the ability of the nerve to respond to **threshold stimulus** by producing an action potential. - During action potential the ability of the nerve to respond to a new stimulus and produces an action potential is changed. ## Phases of excitability: - **Absolut refractory period (ARP):** - It occupies the depolarization and the first third of repolarization. - The excitability is zero - The nerve can not respond to any stimulus whatever its strength. - **Relative refractory period (RRP):** - It occupies the second 2/3 of repolarization. - The excitability is partially recovered but still subnormal. - The nerve can respond to a stimulus that is stronger than normal. # Propagation of nerve impulse (Conduction of action potential) ## In unmyelinated nerve: - It occurs as a local current flow (movement of positive charges) around an impulse in an axon. - Positive charges flow into the area of negativity represented by the action potential ("current sink"). - This flow decreases the polarity of the membrane and produces a local depolarization. When the local depolarization reaches the firing level, a propagated action potential is developed. - A repolarization wave follows the depolarization and propagated in the same direction. ## In myelinated nerve (Saltatory conduction): - Conduction in myelinated axons depends on a similar pattern of circular current flow but here the positive charge jumps from one node of Ranvier to the next because myelin is an effective insulator, and current can not flow through it - It is a rapid process that allows myelinated axons to conduct up to 50 times faster than the unmyelinated fibers. - Node to node transmission as the myelin sheath is impermeable to ions - Faster - Conserves energy (economic) ## Conduction in unmyelinated nerve - Point to point transmission - Slower - Consume energy # Characteristics - **Characteristics of action potential:** - It is followed by excitability changes e.g., ARP, and RRP. Thus, it can not be summated. - It follows all or non law which states that : - **Subthreshold stimulus** produces no action protentional - **Threshold stimulus** induces a maximal action potential. - **Suprathreshold stimulus,** produces the same action potential. - **Thus, action potential has constant amplitude (can not be graded).** - Propagated along nerve at constant intensity. # Local potential (graded potential) ## Electrotonic Potentials, or Local potential - Threshold stimulus produces an action potential. - **Subthreshold stimulus** produces a localized depolarizing potential change(less than 15 mv) that rises sharply and fades with time, called **local potential** or electrotonic potential. - It is non-propagated. - It does not follow all or non law. As the strength of the stimulus is increased, the response is greater due to the increasing addition of a local response of the membrane (graded potential). - It is not followed by refractory period; thus it can be summated, and if reached 15 mV of depolarization (potentia of -55 mV), the threshold potential is reached and an action potential occurs. - Certain communication sites in our body respond to their stimuli by local potential as, receptors, synapses (junctions between neurons), junction between nerve and muscle (neuromuscular junction, or motor-end plate) or secretory gland. - Thus, local potential is also called, receptor potential, synaptic potential, or motor end-plate potential. # Local potential (graded potential) | Local potential | Action potential | |---|---| | Small | Large | | Non-propagated | Propagated | | Graded response <br> Does not follow all or non law → can be graded <br> (The amplitude increases as the stimulus increases) <br> Not followed by refractory period → can be summated <br> receptor, synapse, motor end plate | Amplitude <br> Propagation <br> Form <br> Refractoriness and Summation <br> Site | | All or non-response <br> Follows all or non law → can not be graded <br> (constant amplitude) <br> Followed by refractory period → can not be summated <br> Site: membrane of nerves and muscles | # Student Activity ## True and false - Action potential can be summated. **F** - Conduction of action potential is faster in myelinated than unmyelinated nerve. **T** - Voltage gated K+ channel act in a positive feedback mechanism in action potential. **F** # References - Barrett KE, Barman SM, Brooks HL, and Yuan JX. (2019). Ganong's Review of Medical Physiology. 26th ed. ebook by McGraw-Hill Education. - Hall JE, and Hall ME. (2021). Guyton and Hall Textbook of Medical Physiology. 14th ed. eBook by Elsevier, Inc. - Sherwood L, (2016). Human Physiology From Cells to Systems. 9th ed. eBook by Nelson Education, Ltd. # It's so lovely to meet all of you! - Thank you for listening.