1. Neurons send messages electrochemically à means that chemicals cause an electrical signal 2. Chemicals in the body are “electrically charged” – when they have an electrical charge, they are called ions 3. Important ions in the nervous system are: Sodium (Na+) and Potassium (K+) – both have 1 positive charge 4. Other ions include Calcium (Ca2+) and Chloride (Cl-) 5. There are also negatively charged protein molecules (inside the cell) 6. Important to remember that nerve cells are surrounded by a membrane that allows some ions to pass through and blocks the passage of other ions à called semi-permeable membrane
Resting membrane potential 1. When a neuron is not sending a signal, it is “at rest” 2. Although concentrations of different ions attempt to balance out on both sides of the membrane, they cannot because the cell membrane allows only some ions to pass through channels (ion channels) 3. When cell is at rest, and ion channels are closed (except for leakage channels which randomly open), ions are distributed across the membrane in a very predicable way 4. When a neuron is at rest, inside of the neuron is negative relative to the outside (K+ and A- inside the cell; Na+ and Cl- outside of the cell) à concentration of Na+ ions outside of the cell is 10 times greater than concentration inside à concentration of K+ is greater inside than outside 5. The resting membrane potential of a neuron is about -70mV à means that inside of the neuron is 70mV less than the outside à exact value measured for resting potential varies between cells, but -70 mV is most commonly used as this value 6. At rest, K+ ions can cross through the membrane easily 7. Also at rest, Cl- ions and Na+ ions have a more difficult time crossing 8. The negatively charged protein molecules (A-) inside neuron cannot cross membrane 9. In addition to these selective ion channels, there is a pump that uses energy to move 3 Na+ ions out of the neuron for every 2 potassium ions it puts in, regulating ion concentration on both sides of the cell membrane 10. Leakage channels allow Na+ to slowly move into cells or K+ to slowly move out, and the Na+/K+ pump restores them à may appear to be a waste of energy, but each has a role in maintaining membrane potential 11. Leakage channels: randomly gated, meaning that they open and close at random, hence the reference to “leaking” à there is no actual event that opens these channels à instead, it has an intrinsic rate of switching between the open and closed states 12. Finally, when all these forces balance out, the difference in the voltage between the inside and outside of the neuron is measured, you have the resting potential 13. Resting membrane potential describes the steady state of the cell, which is a dynamic process that is balanced by ion leakage and ion pumping à without any outside influence, it will not change 14. To get an electrical signal started, the membrane potential has to change
Action potentials 1. Action potential occurs when a neuron sends information down an axon, away from the cell body à AP can also be referred to as “impulse” 2. Action potential is an explosion of electrical activity that is created by a depolarizing current (making the inside of the cell more positive) à means that some event (a stimulus) causes resting potential to move towards 0 mV 3. A stimulus first causes sodium channels to open Action Potential and Synaptic Transmission
4. Because the concentration of Na+ is higher outside the cell than inside the cell by a factor of 10, ions will rush into the cell that are driven largely by the concentration gradient (because the cell is trying to “balance” itself out 5. Remember, Na+ has a positive charge so the neuron becomes more positive and becomes depolarized, meaning the membrane potential moves toward zero 6. When depolarization reaches about -55 mV, a neuron will fire an action potential à this is the threshold à if the neuron does not reach this critical threshold level, then no AP will fire 7. Also, when threshold level is reached, an action potential of a fixed size will always fire à for any given neuron, the size of the action potential is always the same (amplitude) à there are no big or small potentials in one nerve cell – all action potentials are same size à therefore, neuron either does not reach threshold or a full action potential is fired – this is the all- or-none principle 8. The concentration gradient for Na+ is so strong that it will continue to enter the cell even after the membrane potential has become zero, so that the voltage immediately around the pore begins to become positive à membrane potential will reach +30-40 mV by the time the Na+ has entered the cell 9. As the membrane potential reached 40 mV, other voltage-gated channels are opening in the membrane à these channels are specific for the potassium ion 10. It takes longer for potassium channels to open 11. When they do open, potassium rushes out of the cell, reversing the depolarization, taking a positive charge with it 12. Also, at about this time, Na+ channels begin to close (no more coming into the cells) 13. Causes action potential to go back towards -70 mV à membrane potential begins to move back toward its resting voltage à this is called repolarization, meaning that the membrane voltage moves back toward the -70 mV value of the resting membrane potential 14. Action potential actually goes past -70mV (hyperpolarization) because K+ ions stay open a bit too long and are delayed in closing so its overshoots that value 15. Gradually, ion concentrations go back to resting levels and cell returns to -70 mV
Synaptic transmission 1. The synapse of “gap” is the place where information is transmitted from one neuron to another 2. Synapses usually form between axon terminals and dendritic spines 3. Neuron transmitting the signal is called the presynaptic neuron, and the neuron receiving the signal is the postsynaptic neuron 4. There are two types of synapses: chemical and electrical
Chemical transmission 1. When an action potential reaches the axon terminal it depolarizes the membrane and opens voltage- gated Na+ channels 2. Na+ ions enter the cell, further depolarizing the presynaptic membrane 3. This depolarization causes voltage-gated Ca2+ channels to open 4. Calcium ions entering the cell initiate a signaling cascade that causes small membrane-bound vesicles, called synaptic vesicles, containing neurotransmitter molecules to fuse with the presynaptic membrane 5. The fusion of a vesicle with the presynaptic membrane causes neurotransmitter to be released into the synaptic cleft, the extracellular space between the presynaptic and postsynaptic membranes 6. The neurotransmitter diffuses across the synaptic cleft and binds to receptor proteins on the postsynaptic membrane 7. The binding of a specific neurotransmitter causes particular ion channels, in this case ligand-gated channels, on the postsynaptic membrane to open 8. Neurotransmitters can either have an excitatory or inhibitory effects on the postsynaptic membrane à for example, when acetylcholine is released at the synapse between a nerve and muscle (called neuromuscular junction) by a presynaptic neuron, it causes postsynaptic Na+ channels to open à Na+ enters the postsynaptic cell and causes postsynaptic membrane to depolarize Action Potential and Synaptic Transmission
à this depolarization is called an excitatory postsynaptic potential (EPSP) and makes the postsynaptic neuron more likely to fire an action potential
à release of neurotransmitter at inhibitory synapses causes inhibitory postsynaptic potentials (IPSP), a hyperpolarization of the presynaptic membrane à for example, when neurotransmitter GABA (gamma-aminobutyric acid) is released from a presynaptic neuron, it binds to and opens Cl- channels à Cl- ions enter the cell and hyperpolarizes the membrane, making neuron less likely to fire an action potential 9. Once neurotransmission has occurred, neurotransmitter must be removed from the synaptic cleft to the postsynaptic membrane can “reset: and be ready to receive another signal 10. This can be accomplished in three ways: à neurotransmitter can diffuse away from the synaptic cleft à neurotransmitter can be degraded by enzymes in synaptic cleft à neurotransmitter can be recycles (sometimes called reuptake) by presynaptic neuron
Electrical synapse 1. While electrical synapses are fewer in number than chemical synapses, they are found in all nervous systems and play important and unique roles 2. The mode of transmission in electrical synapses is quite different from that in chemical synapses 3. In an electrical synapse, the presynaptic and postsynaptic membranes are very close together and are actually physically connected by channel proteins forming gap junctions 4. Gap junctions allow current to pass directly from one cell to the next 5. In addition to the ions that carry this current, other molecules, such as ATP, can diffuse through the large gap junction pores
6. There are key differences between chemical and electrical synapses 7. Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels 8. Additionally, this signaling is unidirectional 9. Signaling in electrical synapses, in contrast, is virtually instantaneous (which is important for synapses involved in key reflexes), and some electrical synapses are bidirectional 10. Electrical synapses are also more reliable as they are less likely to be blocked, and they are important for synchronizing the electrical activity of a group of neurons 11. For example, electrical synapses in thalamus are though to regulate slow-wave sleep, and disruption of these synapses can cause seizures
Signal summation 1. Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron, but often multiple presynaptic inputs must create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential 2. This process is called summation 3. Additionally, one neuron often has inputs from many presynaptic neurons – some excitatory and some inhibitory – so IPSPs can cancel out EPSPs and vice versa 4. It is the net change in postsynaptic membrane voltage that determines whether the postsynaptic cell has reached its threshold of excitation needed to fire an action potential 5. Together, synaptic summation and the threshold for excitation act as a filter so that random “noise” in the system is not transmitted as important information