unit 4: physiology, neurochemistry, and pharmacology of neurons Flashcards
inside and outside axon
more K+ concentrated inside the cell than outside and there is more Na+ concentration outside the cell than inside
electrostatic forces and diffusion potential
Hodgkins and Huxley found that the basis of the action potentials they measured was the movement of sodium and potassium ions across the cell membrane.
Because of the differences in concentrations of different ions inside the nerve cell vs outside the nerve cell, there are two forces on the ions to make the ions want to move.
The two main forces that drive movement of ions across cell membranes are electrostatic forces and diffusion.
– electrical charges want to equilibrate!
– chemicals want to equilibrate!
relative concentration of ions and contribution to resting membrane potential
The electrical difference between the outside and inside of the cell is called a “potential” it is the difference
The difference is across the membrane, so it is called the “membrane potential”
When the neuron is at rest – not communicating, this difference is called the “resting membrane potential”
ion pump is coupled
it pumps sodium ions out of the cell and potassium ions in. It used considerable biological energy in the form of adenosine triphosphate (ATP) because it must pump both ions against their concentration gradients. Since it is a protein, its activity is determined by the concentration of its “substrate,” which is sodium ions inside and potassium ions outside. The more sodium inside the cell, the more active the pump becomes—a perfect example of a self-regulating system. adenosine diphosphate = ADP
factors that establish the resting membrane potential
The distribution of charged ions difference between the inside (intracellular) and outside (extracellular) space of neurons
Sodium-potassium pump keeps neurons in the resting state
Electrostatic forces and diffusion potential are the forces that will ultimately determine ion movement across the cell membrane
“injecting” current into cells
Changes in neuron membrane potential can be induced artificially by “injecting” current into the cell. By injecting negative vs. positive current into the cell, you can make the potential difference across the membrane either more or less respectively, manipulate the cell membrane
excitatory potential (EP)
cells start to become depolarized (inside is increasingly positive)
inhibitory postsynaptic potential (IP)
cell becomes hyperpolarized (inside is increasingly negative)
depolarization
decrease in potential; membrane less negative
repolarization
return to resting potential after depolarization
hyperpolarization
increase in potential; membrane more negative
increasing positive current into the cell
makes the difference between inside and outside the cell less, so the cell is less polarized = depolarization
the cell returns to resting level
making the inside more negative again and thus more polarized = repolarization
decremental conduction of membrane potential change down an axon
The voltage response in a passive neuronal process decays with distance due to electronic conduction. Current injected into a neuronal process by a microelectrode follows the path of least resistance to the return electrode in the extracellular fluid (A). The thickness of the arrows represents membrane current density at any point along the process. Under these conditions the change in Vm decays exponentially with distance from the site of current injection (B). The distance at which Vm has decayed to 37% of its value at the point of current injection defines the length constant, .
Decremental conduction. When a subthreshold depolarization is applied to the axon, the disturbance in the membrane potential is largest near the stimulating electrode and gets progressively smaller at distances farther along the axon.
The further you get away from the stimulus the lower the amplitude gets, this can be measured up and down the axon, the current depolarizes as it moves further away
neurons are sensitive to stimuli
- For example, to mechanical and chemical stimuli and to voltage changes across the cell membrane
- Stimuli can cause the opening or closing of ion channels
- Ions cant diffuse across membranes. They use channels or “pores” so we need to know what can cause ion channels to open and close
voltage-gated ion channels
Voltage dependent channels change their shape when the potential difference becomes sufficiently positive. The figure shows a channel protein molecule with voltage sensing dominas and a pore domain. You can just see aspects of the pore domain move in response to the change in electrical potential of the membrane
Some ion channels are sensitive to the electrical potential difference across the cell membrane
Voltage-gated sodium and potassium channels open when the PD becomes sufficiently positive
opening and closing of voltage gated channels
Left: Voltage-gated ion channels are responsive to changes in the membrane potential itself. If the electrical potential across the cell membrane changes enough (depolarizes enough) the pore opens and the ion can move. Note: there is a brief refractory period during which the channel will not open. Note the “ball and chain” component of the channel that is involved in plugging the channel during the refractory period.
Right: The movements of ions during the action potential. The shaded box at the top shows the opening of sodium channels at the threshold of excitation, their refractory condition at the peak of the action potential, and their resetting when the membrane potential returns to normal.
conduction of an action potential
When an action potential is triggered, its size remains undiminished as it travels down the axon. The speed of conduction can be calculated from the delay between the stimulus and the action potential
The action potential is conducted away from the origin via a series of local depolarizations of membrane tissue. The entry of sodium via sodium channels at one segment of membrane quickly is sufficient to depolarize the adjacent piece of tissue so that sodium channels open there. This perpetuates down the length of the axon.
There is a catch: it takes time for each segment to depolarize enough to open channels in the segment next to it. This makes propagation of an electrical signal down the length of the neuron a relatively slow process. Note: 100 ms to go 1 meter.
saltatory conduction
In neurons with a myelin sheath, the action potential appears to jump down the length of the axon at a much faster rate. This is saltatory conduction. The trick is that myelinated axons use basic electrical “cable properties” for quick propagation of the signal under the myelinated lengths and rejuvenation of the action potential signal at the intervening nodes of Ranvier.
Recall that current injected into a passive neuronal process decays with distance. However, it is quick. The tissue under the myelin is passive. Therefore, current injected by the action potential travels quickly under the myelin via cable properties and also decays quickly. However, just before the current dies away, it encounters a node of Ranvier with sufficient remaining voltage to cause depolarization. Thus, the signal is renewed and the process is repeated down the entire length of axon. Note: 7 ms to go 1 meter!
multiple sclerosis
Neurological disease
Degeneration of myelin sheath
Autoimmune disease
Myelin basic protein
It is unknown what specifically about myelin is being attacked, but speculation is that the “myelin basic protein” (MBP) is under attack. The MBP maintains the correct structure of myelin by interacting with lipids in the myelin membrane.
spatial summation
A neuron might receive stimulatory input simultaneously from three different sources, i.e., the three tiny crosses.
Each stimulatory graded potential from the three individual sources is too small to be effective. But if their small depolarizations arrive at the axonal hillock at the same time, they activity may summate sufficiently to trigger ann action potential.
Trigger zone = axon hillock = initial segment
temporal summation
A single source may be able to initiate a response if it sends enough signals in a short-enough time
Individual excitatory graded potentials rapidly decay. However, if multiple graded excitatory potentials happen quickly enough, the effect summates as the next one causes additional depolarization before the previous one can decay
If you don’t have voltage gated channels that allow salt into the cell then an action potential cannot occur
movement of negatively charged ions into the cells or positively charged ions out of cells causes hyperpolarization
Neurons are not affected only by stimuli that excite them. There is inhibitory input as well. There is inhibitory input as well. The generation of an IPSP can be caused by inward flow of negatively charged chloride ion or outflow of K+. recall from the earlier table; there is much more chloride ion outside the cell, so opening a channel permits chloride to flow in and also that there is more K+ inside that opening a K+ channel allows more K+ to flow out
spatial and temporal summation
The decision by a neuron to fire is a consequence of simultaneous integration of information from multiple excitatory and inhibitory inputs. Note the electron microscopic picture of a neuron with attached terminal buttons
neural integration
If several excitatory synapses are active at the same time, the IPSPs they produce (shown in red) summate as they travel toward the axon, and the neuron fires. (b) If several inhibitory synapses are active at the same time, the IPSPs they produce (shown in blue) diminish the size of the EPSPs and prevent the axon from firing.
if the momentary membrane potential ever surpasses the threshold for excitation
an action potential is generated
neurotransmission
communication between neurons
- Occurs at the level of the synapse, or the junction between presynaptic and postsynaptic neurons
- Neurotransmission involves the release of endogenous ligands known as neurotransmitters and neuromodulators
- Neurotransmitters and neuromodulators bind to receptors to alter neuron function
final pathways of a somatic motor neuron and ANS motor neuron
Chemical transmission at a nerve muscle synapse. In this famous experiment performed in 1921, otto loewi placed an innervated and non-innervated heart in two separate chambers connected by a bridge of physiological saline. At the bottom is shown the rate of beating of both hearts before and after stimulation of the vagus nerve connected to the first heart
Vagusstoff = acetylcholine
ligand
receptors interaction conceptualized as a “key in lock” or better as “hand in glove”
