NEUROPHYSIOLOGY

The Resting Cell Membrane Potential

All cells exhibit an electric potential (voltage) called the Resting Cell Membrane Potential. They measured this voltage and found it varies in cells from 70-90mV, usually its written as 70mV or 90mV because its a negative voltage.

Where does this voltage come from?

The difference between the Na+ outside the cell and the K+ Proteins inside the cell are what create the difference in electrical polarity.

How come almost all the potassium is inside of our cells and all the sodium is outside?

Sodium-Potassium ATP

Do all molecules affect the electrical polarity of the cell?

NO!

Physiological Basis of the Resting Cell Membrane Potential

The cell membrane is often described as being semi-permeable . Cell membranes are normally permeable to K+ but not to Na+ or any other electrolyte.

Why does potassium flow out of a cell?

Because of a concentration gradient

Why doesnt potassium flow out of the cell until there are equal amounts inside and out?
Normally chemicals diffuse until their concentrations are equal everywhere As potassiums flow out due to the concentration gradient, the inside of the cell becomes more negative, which attracts the potassium (K+) back inside the cell because opposite charges attract and the potassium ion channels are always open.

Two FORCES acting on K

1) The concentration gradient causes K+ to diffuse out of the cell. 2) The electrical gradient that develops, causes K+ to diffuse back into the cell. The equilibrium (steady-state) potential of 90mV is called the resting cell membrane potential (voltage)

What is Hypokalemia?
The Effects of Hypokalemia
fatigue, muscle weakness (including respiratory muscles), weak, irregular heart beat and decreased GI motility

Who develops hypokalemia? What causes hypokalemia?

1) Inadequate intake of potassium 2) The use of diuretics 3) Excessive vomiting or diarrhea, especially in infants 5) Profusive sweating a

What is Hyperkalemia?
The Effects of Hyperkalemia 1) irritability and anxiety 2) muscle twitches 3) heart flutters and fibrillations 4) increased GI motility

Who develops hyperkalemia? What causes hyperkalemia?

1) Kidney failure 2) 2) Excessive IV administration of K+.

Treatment for Hyperkalemia

Give diuretics Give ion-exchange resin Hemodialysis

What is an Action Potential? (Nerve Impulse)

An action potential, or nerve impulse, is a transient (short lasting) reversal in the membrane potential that is conducted down the length of the fiber.

Events of the Action Potential

1) When we stimulate an excitable cell, Na+ ion channels are going to open up and sodium is going to rush into the cell 2) So how does the cell repolarize back?

OVERVIEW
1. Depolarization: Membrane potential becomes less polarized than normal
Stimulus ->Increased permeability of sodium ion channels -> Na+ rush into cell -> Depolarization

2. Repolarization: Return of the membrane potential back towards the normal resting state.
Increased permeability of potassium ion channels -> K+ rushes out of the cell -> Repolarization

3. After-hyperpolarization: Membrane potential becomes even more polarized (negative) than normal
Results from more potassium diffusing out of the cell than the sodium that had diffused in.

4. Re-establishment of the Na+ & K+ concentration gradients.

The Na+/K+ ATP pumps use energy to rapidly transport Na+ ions out of the cell and K+ into the cell.

Electrical Refractory (Recovery) Period following an Action Potential The electrical refractory (recovery) period (R.P.) is the period of time following an Action Potential when the cell will not respond to another stimulus.

Why is the Refractory Period important to know?

The length of the cells electrical R.P. determines the maximum frequency of APs it can generate. In this nerve cell, it can generate about 1 AP every 10 milliseconds. 1 AP / 10msec X 1000 msec / sec = 100 APs / sec

Subthreshold, Threshold and Suprathreshold Stimuli

Conduction of the Action Potential along the Nerve Fiber

Conduction along an Unmyelinated Nerve Fiber

Conduction along a Myelinated Nerve Fiber

Conduction Velocity in nerve fibers

1) whether its myelinated or umeylinated. (In a myelinated neuron, the AP travels faster. ALL muscle cells are unmyelinated while nerve cells could be either.) 2) The larger the diameter of the nerve fiber, the faster the conduction velocity.

Synaptic Transmission by Somatic Motorneurons

Synaptic Transmission by Somatic Motorneurons

Whats going on at the Neuromuscular Junction.

Synaptic Transmission at the Neuromuscular Junction

1. An Action Potential (AP) is conducted down the somatic motorneuron down to the synaptic knob. 2. The reversal in electrical polarity at the synaptic knob causes an opening of voltage-gated Ca+2 channels (Voltage gated calcium ion channels open and allow calcium ions to flow inside due to the voltage change). Calcium ions are very important for the release of neurotransmitters and secretion of hormones by endocrine cells. 3. Calcium flows into the synaptic knob and its this influx that causes these vesicles to form and release/secrete neurotransmitters. In other words, the entry of Ca+ into the synaptic knob causes the exocytosis (secretion) of the nerotransmitter Acetylcholine (ACh). 4. The ACh diffuses across the synaptic cleft and binds to nicotinic ACh Receptor Site Proteins on the membrane of the Skeletal Muscle Cell (Fiber). The first chemical they discovered that affects this receptor site, happened to be nicotine so thats why it got the name, nicotinic cholinergic receptor. 5. Activation of the ACh Receptor Sites causes an opening of ligand-gated Sodium Ion Channels.

Synaptic Transmission at the Neuromuscular Junction

6. As sodium ions flow into the Skeletal Muscle Cell, it depolarizes to the threshold potential, triggering an Action Potential. 7. As the action potential spreads along the cell, it causes the muscle cell to contract. 8. The ACh which is attached to the receptor site, is split into acetate and choline by acetylcholinesterase (ACHase), an enzyme of the skeletal muscle cell membrane. 9. The ligand-gated sodium ion channels close, permitting the skeletal muscle cell to relax. 10. The acetate & choline are actively transported back-up into the synaptic knob (Active Reuptake) to be re-synthesized.

Synaptic Transmission by Sensory Neurons

1. Each synaptic neurons typically synapses onto hundreds of other neurons, they usually synapse onto interneurons but may synapse directly to motor neurons. 2. Sensory neurons always act to excite the post synaptic neurons

Synaptic Transmission by Interneurons

1. Each interneurons typically influences some other 100 neurons. 2. The conduction of AP along a neuron, trigger the release of neurotranmitter from its synaptic knobs 3. Each interneuron trigger the release of I one neurotranmitter

Actions of Excitatory and Inhibitory Neurotransmitters

Action of Excitatory Neurotransmitters
Some neurons in the CNS release neurotransmitters that excite other neurons (meaning to fire off APs) and some inhibit (prevent) the generation of action potentials.

Action of Excitatory Neurotransmitters

ALL excitatory neurotransmitters cause an opening of ligand-gated sodium ion channels. These excitatory neurotransmitters create a local increase of permeability of sodium ion channels (ligand gated sodium channels open) which leads to a local depolarization thats known as an Excitatory Postsynaptic Potential (EPSP)because we are exciting the post-synaptic cell.

Action of Inhibitory Neurotransmitters

When an inhibitory NT activates the receptor site, it causes additional potassium channels to open which may cause potassium ions to flow out of the celland if additional positively charged potassium ions flow out of the cell, the inside of the cell will become more negative. In other words, inhibitory neurotransmitters cause an opening of ligand-gated potassium ion channels which leads to a local hyperpolarization (more negative than normal). This is known as a Inhibitory Postsynaptic Potential (IPSP) because its going to beLESS likely to throw off an action potential. The inhibitory NT could also cause an opening up of ligandgated Chloride Ion channels. Chloride is mostly outside the cell and its negatively charged. When these channels open, negatively charged ions will flowinside the cell, making it more negative (local hyperpolarization).

Summation of Post-Synaptic Potentials

So whats this postsynaptic neuron going to do if both these EPSP and IPSPs are firing off together?

Temporal Summation
Temporal summation is the summation of EPSPs or IPSPs due to repeated stimulation by one neuron. Stimuli applied to the same axon sufficiently close together in time add together to depolarize the membrane.

Spatial Summation
Theres also something called spatial summation which is the summation of EPSPs or IPSPs due to stimulation by more than one neuronsimultaneously.