Supplemental Study Notes for Neurophysiology
1. Excitable cells like nerve and muscle need to 'know' when they are supposed to do something, e.g., send a nerve impulse, contract.
2. The way cells in the body accomplish this is by using the flow of cations or anions through the cell membrane.
3. However, remember that in order for ions to flow from one place to another, there must be a concentration gradient in which there is a higher concentration of ions in one place vs. the other.
4. This means that in order for a cell to be in a 'ready' state to know that it's being stimulated, it must always maintain an unequal concentration of specific ions on the inside and outside of the cell membrane.
a. Recall that Na+ is in high concentration outside cells, and low concentration inside cells. This creates a Na+ gradient in which Na+ can potentially flow from outside to inside cells.
b. Recall that K+ is in high concentration inside cells, and low concentration outside cells. This creates a K+ gradient in which K+ can potentially flow from inside to outside cells.
c. The difference in the concentration of ions on different sides of the plasma membrane creates a transmembrane potential. This means the cell membrane is polarized, and is in a ready state to be signaled to do something.
d. Recall that the inside of the plasma membrane is negative compared to the outside. This difference, which is about - 70 millivolts (mV) in neurons, is the resting transmembrane potential.
e. The negative ions that balance the positive ions outside the cell are mainly Cl-. Inside the cell, the major negative charges come from proteins, which have side chains (remember R groups?) that have a net negative charge.
i. Cl- ions are small enough that they can fit through channels in the cell membrane, so sometimes these pass from outside to inside the cell, i.e., down their concentration gradient, when an appropriate channel opens.
ii. Proteins are too big to pass through membrane channels and remain trapped inside cells.
5. Remember that the plasma membrane of cells is constructed from phospholipids, fatty material which does not allow the passage of polar molecules like Na+ and K+ ions.
a. In order for these ions to travel from one side of the cell membrane to the other, there must be hydrophilic channels for them to pass through.
b. When these channels open and allow ions through, facilitated diffusion is taking place.
6. Several types of channels exist that allow passage of Na+ and K+. These include:
a. Leak channels (Passive) - these are always open. This means that ions can continually flow through these channels, as long as there is a gradient driving the flow of these ions.
b. Active, or gated, channels - these are normally closed and need something to open them. These channels are classified according to the thing, or event, that opens them. There are three major types:
i. Mechanically gated channels open in response to something 'deforming' the cell membrane.
- A good example is found in touch/pressure receptors in the skin. When the skin is pressed, the cell membrane of these receptors deforms and the channels open.
ii. Ligand gated channels. Ligand is another name for 'chemical'. This means that the 'key' that opens these channels is a chemical which must first bind to the receptor. After the ligand, e.g., acetylcholine, is bound the channel opens briefly to allow ions like Na+ to pass from one side of the cell membrane to the other.
iii. Voltage gated channels. These channels open in response to some change in the pre-existing membrane potential.
- For example, if the membrane potential of a neuron increases from -70 mV to -60 mV, the voltage gated channels for Na+ will open.
- This 'magic' membrane potential that opens the voltage-gated Na+ channels in a neuron is called the threshold.
7. How the resting transmembrane potential of neurons is created
a. K+ leak channels in the neuron cell membrane are always open and allow the continual leakage of K+ from inside the cell to the outside.
i. K+ are positively charged, so every time one of these positive charges leaves the cell, the inside of the cell membrane becomes a little more negative.
ii. K+ ions continue to flow out of the cell until the inside of the cell membrane has a charge of - 70 mV. This is the resting transmembrane potential of the neuron. In this state, it's ready to be stimulated, e.g., by another nerve. Thus, the flow of K+ through K+ leak channels is what establishes the neuronal resting membrane potential.
iii. Some Na+ also leaks into the cell normally. However, the amount of Na+ that comes into the cell is much less than the amount of K+ leaving the cell.
b. In the membrane of the neuron are Na+-K+ ATPase pumps whose job it is to maintain the correct membrane potential. They do this by in two ways:
- Bringing K+ that has leaked out of the cell back into the cell.
- Ejecting Na+ out of the cell that has leaked into the cell.
8. How the depolarization of a nerve impulse (action potential) is triggered
a. A single neuron is continually bombarded with input from other neurons. This bombardment comes in the form of chemical synaptic transmission:
i. A neurotransmitter (ntx) is released into the synaptic cleft
ii. The ntx binds to LIGAND-GATED channels on the nerve cell being stimulated
iii. After binding the ntx, the ligand-gated channels open very briefly and then close. When they are open, a small amount of Na+ leaks into the cell.
- Since Na+ is positively charged, every time a Na+ enters the cell the membrane potential of the cell being stimulated goes up toward more positive values.
- Movement of the membrane potential up toward more positive values is called depolarization.
- These small deviations away from resting membrane potential are called local (graded) potentials.
- They may, or may not, be sufficient to cause the stimulated cell to fire an action potential since the membrane potential has to reach threshold before an action potential is generated.
b. If threshold is NOT reached, the Na-K ATPase pumps eject the small amount of Na+ that came into the cell, and the resting membrane is restored.
c. If threshold IS reached, the VOLTAGE-GATED Na+ channels in the intial segment of the neuron open and the neuron is flooded with Na+, rapidly raising the membrane potential to zero and above. This is the depolarization of an action potential (nerve impulse).
i. There is so much Na+ flooding the cell at this point that the Na-K ATPase pumps are overhwhemed and cannot eject the Na+ as fast as it's entering the cell.
ii. This causes Na+ to accumulate in the neuron.
9. How repolarization is carried out
a. During depolarization, as the membrane potential of the stimulated nerve reaches a certain positive value, voltage-gated K+ channels open. Around the same time, the Na+ channels close and stop the inward flow of Na+.
b. K+ flows rapidly down its concentration gradient through the open voltage-gated K+ channels and leaves the cell. Since K+ is a postively charged ion, each time a K+ leaves the cell, the membrane potential becomes a little more negative and begins to return toward negative values. This movement of the membrane potential toward more negative values is called repolarization.
c. As the membrane potential nears the normal - 70 mV resting potential, the K+ slowly begin to close, but not before too much K+ has leaked out of the cell and causes a slight hyperpolarization.
d. The hyperpolarized cell now has an improper balance of ions, compared to a resting neuron. This is corrected by the Na-K ATPase pumps (see how above), and the neuron returns to its resting membrane potential.
10. Absolute and Relative refractory periods
a. The period of time spanning depolarization and most of repolarization is known as the absolute refractory period.
i. During this period, the neuron cannot be stimulated to generate another action potential.
ii. The absolute refractory period is responsible for the fact that the nerve impulse travels in one direction in an axon, i.e., away from the soma and toward the synaptic knobs.
b. The period of time immediately following the absolute refractory period is known as the relative refractory period.
i. This coincides with the period during which the neuron is hyperpolarized.
ii. Since the membrane potential during hyperpolarization is further away from threshold than normal, it takes a larger than normal stimulus to stimulate the neuron to generate another action potential.
11. EPSP and IPSP
a. An Excitatory Post-Synaptic Potential (EPSP) raises the membrane potential toward more postiive values and moves the membrane potential closer to threshold, i.e., this is a depolarization.
b. An Inhibitory Post-Synaptic Potential (IPSP) lowers the membrane potential toward more negative values and moves the membrane potential further away from threshold, i.e., this is inhibition.
12. Chemical Synaptic Transmission
a. This is the method by which neurons communicate with one another and with other structures, e.g., muscle, glands, etc.
b. It involves release of a ntx stored in synaptic knobs from one neuron (pre-synaptic neuron) across a synapse, and then binding of the ntx to the receptors/channels on the next neuron in the pathway (post-synaptic neuron).
c. Ntx is released from vesicles in the synaptic knob.
- A nerve impulse traveling down the axon of a pre-synaptic neuron causes voltage-gated Ca2+ channels in the vicinity of the synaptic knob to open. Ca2+ flows into the neuron and causes the vesicles to fuse with the plasma membrane. This fusion results in release of the ntx into the synaptic cleft.
d. Ntx travels across the synapse and binds to the channels on the post-synaptic membrane.
e. Binding of the ntx opens channels in the post-synaptic neuron and results in ion flow across the plasma membrane.
f. This causes a local (graded) potential to occur. (See above to understand the role of local potentials to cause an action potential to be generated.)
In order to test your understanding of the concepts described above, complete item 18 from Lecture 18 on the Study Guide (without looking at your notes of course!).