BBT 221 Lecture 6: Nervous System PDF

BBT 221 Summer 2024 TSHq Lecture 6 Topic 4: Nervous system (Vander, chapter 6, and Silverthorn, chapter 8) POTENTIAL DIFFERENCE - A potential difference (or just “potential”) is the difference in the amount of charge between t...

BBT 221 Summer 2024 TSHq Lecture 6 Topic 4: Nervous system (Vander, chapter 6, and Silverthorn, chapter 8) POTENTIAL DIFFERENCE - A potential difference (or just “potential”) is the difference in the amount of charge between two areas. It occurs from a separation of charges. - The unit to measure potential difference is called “volts” (V). - In biological systems, the potential differences are very small, so we measure them in mV (millivolts). - When there is a potential difference, opposite charges will usually move as they are attracted to each other. - This movement of charges is called a current MEMBRANE POTENTIAL - The intracellular fluid of a cell has a different ion concentration than the interstitial fluid. - The outside and inside of the cell therefore has a difference in charge. - The two sides of the membrane are in electrical disequilibrium. - So, there is a potential difference on the two sides of a cell membrane. - This potential difference at any given time is called the MEMBRANE POTENTIAL STING MEMBRANE POTENTIAL - When a cell is at rest and everything is stable (there is no stimulus), its membrane potential is called the “RESTING MEMBRANE POTENTIAL” - For most cells, including nerve cells and muscle cells, the resting membrane potential is around – 70 mV. - This means that the INSIDE of the cell is 70 mV more negative than the outside of the cell - Why and how is the inside of the cell more negative?  Remember the Na+/K+ pump, which pumps out 3 positive charges (Na+) and pumps in only 2 positive charges (K+). - The Na+/K+ pump is one of the things that ensures - At rest, there are more negative ions on the inside of the cell remains negative compared to the outside. Ion channels also help maintain resting the inside of the cell, more positive ions on membrane potential the outside of the cell. - Besides Na+ and K+, the movement of Cl- also - The opposite charges attract and collect contributes to this around the membrane - This area around the membrane therefore has a small potential difference. - Most of the fluids everywhere else are usually overall neutral - Ion movement across the membrane will depend on electric gradient, concentration ECTRICAL ACTIVITY IN AXONS - When the membrane potential of a cell changes from resting potential, electric signals are produced. - This happens due to a change in the movement of ions across the cell’s membrane. - If we place a voltmeter to detect the changes in the membrane potential (ie- measure how different the charges inside the cell is compared to the outside), we can detect these changes. - The resting potential is -70 mV. This can change in several ways after the neuron is excited 1.(stimulated). DEPOLARIZATION: The membrane potential can become more positive (closer to 0). This means the potential difference has been reduced as the voltage inside of the cell is closer to the voltage outside of the cell 2. REPOLARIZATION: The membrane potential comes back to the resting potential (of around -70 mV) 3. HYPERPOLARIZATION: The membrane potential becomes even more negative than the resting potential. The potential difference between the inside and outside of the cell has increased. RADED POTENTIAL - When a stimulus is detected, a cell membrane’s ion channels will open/close and change the cell’s permeability to different ions to change - This causes different ions to enter/leave and the membrane potential to change by a small amount of depolarization or hyperpolarization - The change in membrane potential are confined to a small region only. - The cell becomes repolarized soon and no signal is transmitted. A small section of the cell got depolarized/hyperpolarized, and then repolarized again, and that’s it. The stimulus was not big enough to initiate electrical impulses across the cell. - These are called GRADED POTENTIALS - A single graded potential usually dies out and does not cause a response. - However, if additional stimuli occur before the graded potential has died away, these can be added to the depolarization from the first stimulus. - This process is called summation. - If the resulting potential difference (ie- CTION POTENTIAL - Nerve and muscle cells as well as some endocrine, immune, and reproductive cells have plasma membranes capable of producing action potentials. These are called EXCITABLE MEMBRANES. - If the membrane is depolarized to around 55 mV, the signal is usually strong enough to cause a response through an ACTION POTENTIAL - This minimum voltage needed to be reached for an action potential is called the THRESHOLD POTENTIAL. Only a strong enough stimulus will cause this so we are not reacting to every small random thing. - An action potential will cause an electric impulse to travel along the cell and then be passed on to the next cell, eventually causing a response. This is the long-distance “electric messaging system” of our nervous system Once the membrane potential reaches the threshold value, it is depolarized and then overshoots to a “peak” value. This is called an action potential. Then it is repolarized and there is a period of hyperpolarization called the refractory period. No more action potentials can be generated during this time. Finally, resting membrane potential is restored. Details on next slide. TEPS OF AN ACTION POTENTIAL 1: Cell is in resting membrane potential (-70 mV) 2: A stimulus causes depolarization and the membrane potential eventually reaches the threshold value (-55 mV) 3: Depolarization continues rapidly and the membrane potential keeps decreasing (closer to 0). 4: The membrane potential overshoots and becomes positive compared to the outside of the cell. It reaches a peak value (around +30 mV). 5: After this, the cell start to repolarize and return towards its resting membrane potential. 6: Right after the action potential ends, there is a brief period of hyperpolarization where the membrane potential becomes even more negative than the resting membrane potential. This time is called the REFRACTORY PERIOD. No other action potentials can be generated during these moments ECHANISM OF ACTION POTENTIAL - Ligand gated ion channels: Protein channels on the cell membrane that open or close depending on the binding of a ligand - Mechanically gated ion channels: Protein channels on the cell membrane that open or close if there is any physical change (like stretching) of the cell - Voltage gated ion channels: Protein channels on the cell membrane that open or close depending on the membrane potential of the cell - For action potential propagation, mainly voltage-gated Na + and K+ channels are used (THESE ARE NOT THE Na+/K+ PUMP) - During resting membrane potential, Na+ ion channels and K+ ion channels are usually closed - - The initial stimulus that causes the membrane to depolarize (usually through ligand-gated and mechanically gated ion channels) makes the membrane potential less negative. This happens through facilitated diffusion - This depolarization causes some voltage-gated sodium channels to open in the area of the cell membrane where depolarization took place - So now, more Na+ ions can enter the cell. This causes more depolarization, which causes even more Na+ ion-channels to open as they are voltage-dependent. This causes more depolarization (as positive charges enter the cell more and more). - This is a type of POSITIVE FEEDBACK LOOP (Initial depolarization eventually causes even more depolarization). Usually happens at the threshold voltage. - Depolarization also causes voltage-gated K+ ion channels to open. However, this process is much slower. By the time the K+ ion channels open, the cell is already at its peak value of the action ONSHIP BETWEEN ACTION POTENTIAL AND VOLTAGE-GATED CHANNELS 1: Membrane at resting potential 2. Initial stimulus causes depolarization (usually by mechanical and ligand-gated channels) 3: During depolarization, Na+ channels open quickly. Na+ enters the cell causing even more depolarization. 4: When peak value is reached, K+ ion channels open slowly, causing K+ ions to leave the cell. This leads to repolarization. 5. As membrane potential becomes more and more negative, Na+ channels close quickly. No more Na+ entering the cell 6. K+ channels stay open a bit longer. K+ keeps leaving the cell, causing hyperpolarization (refractory period) Na+ enters cell down its concentration gradient K+ leaves cell down its concentration gradient 7. Finally, K+ channels also close due to the R NOTHING: THRESHOLD POTENTIAL AND PEAK VOLTAGE - Excitable cells follow an all-or-none rule - They will either complete the entire action potential, or not get excited at all - The action potential will ONLY take place if threshold voltage is reached. Any depolarization below the threshold value (called subthreshold potentials) will not result in an action potential as the positive feedback loop of Na+ ion channels is not activated yet. - Once threshold potential is reached, there is no going back. The entire action potential will take place - This means that the peak value will always be reached - No action potential will ever stop midway without reaching the peak value - After threshold potential is reached, repolarization will not take place until after the peak value is reached. - All the action potentials generated in one cell will have the exact same pattern (same threshold, same peak, same refractory period, etc.) - Once threshold is reached, the initial stimulus strength OLE OF NA+/K+ PUMP - Even though the sodium-potassium pump ATPase does not directly play a role in action potential propagation, the action potential would not be possible without it. - The concentration of Na+ inside the cell always has to be kept lower to allow the Na+ to diffuse in during depolarization - This is possible thanks to the Na+/K+ pump always Extracellular space pushing 3 Na+ ions out of the cell - Otherwise, after an action potential, the Na+ concentration inside the cell would keep increasing and there would be no more concentration gradient and no more action potentials! - Similarly, The concentration of K+ inside the cell always has to be kept higher to allow the K+ to diffuse out during repolarization Intracellular space - This is possible thanks to the Na+/K+ pump always pushing 2 K+ ions into the cell - Otherwise, after an action potential, the K+ concentration inside the cell would keep decreasing and there would be no more concentration gradient and no more action potentials! EMENT OF ACTION POTENTIAL ACROSS A NEURON - In afferent neurons, the initial depolarization to threshold is achieved by a graded potential which is generated in the sensory receptors at the peripheral ends of the neurons by stimuli to sensory receptor cells. - In all other neurons, the depolarization to threshold is due either to a graded potential generated by synaptic input to the neuron (we will see this in the next lecture). This ensures the current only flows in one direction. - The action potential is not localized to just one part of the cell, it spread across the cell as Na+ channels all across the cell open up. - Axons are myelinated. Myelin is an insulator that makes it more difficult for charge to flow between intracellular and extracellular fluid compartments, so a local current can spread farther along an axon, making the rest of the cell positive. - There are not many voltage-gated sodium channels in the myelinated region of axons. They are mostly in the gaps between the myelin. These gaps are called NODES OF RANVIER. Here, the positive feedback loop is intensified as more Na+ ions enter the cell - Action potentials occur only at the nodes of Ranvier, where the myelin coating is interrupted and the concentration of voltage-gated sodium channels is high - Thus, action potentials jump from one node to the next as they propagate along a myelinated fiber, but the positive charges (ie- depolarization) that entered here can move through the cell without leaking out, and cause the Na+ channels at the next Node of Ranvier to open. - This “jumping” is called saltatory conduction. NODES OF RANVIER AND SALTATORY CONDUCTION