Ion Channels are responsible for the membrane potential.

When the ion channel is closed, there is no potential difference across the cell membrane

Ion Channels are responsible for the membrane potential.

When the cation-selective ion channel opens, cations will diffuse through, whereas anions will not

Ion Channels are responsible for the membrane potential.

The crossing-over of cations will create a potential difference (voltage) across the cell membrane.

Simulation of membrane:

The Nernst Potential.

These qualitative demonstrations can be put in more quantitative terms using the Nernst Equation, which relates the voltage V across the membrane which is in equilibrium with the concentration gradient established by the concentrations Co, outside, and Ci, inside.

Utility of learning about Nernst potentials:

Characterization of mechanisms of disease.

In This case:

- Learning more about a new ion channel that causes neurons to die during anoxia.

Utility of learning about reversal potentials

C ontrol (n=4) N aCN 2 hr (n=6)

Characterization of a cation current in anoxic neurons

Back to the Axon & How it works

1. Ion Channels

2. Concepts of Diffusion

3. Basic Concepts of Electricity

4. How to Put 1-3 Together

Equivalent circuit of the membrane

Cm = membrane capacitance (in pF)Rm = membrane resistanceEm = Vm = Trans-membrane potential differenceRm = 1/Gm Gm = membrane conductance

Generation of the AP

The action potential is produced through the sequential activation and inactivation of sodium and potassium channels in the axon.

As the membrane depolarizes, Na channels open, allowing an inward Na current to occur. Then, K Channels open, to repolarize the cell while Na Channels inactivate.

Generation of the AP

Generation of the AP

Generation of the AP

Generation of the AP

Generation of the AP

Generation of the AP

Propagation of the AP

Must now take into account the 3D geometry of the Axon.

Propagation of the AP

Simplified into an equivalent circuit that can be mathe-matically analyzed

Simulation: AP Propagation

We have covered:

1. Ion Channels

2. Concepts of Diffusion

3. Basic Concepts of Electricity

4. How to Put 1-3 Together to get propagation of nerve imulses

Now: Back to our patient…..

The Arterial Line is in …

Now we have to put the patient to sleep: General Anesthesia

Now we have to put the patient to sleep: General Anesthesia

Now we have to put the patient to sleep: General Anesthesia

Now we have to put the patient to sleep: General Anesthesia

How General Anesthesia is done:

1. Give patient something to make them sleep (Anesthetic)

2. Give patient something to relax (muscle relaxant)

3. Intubate / Ventilate

4. Monitor them throughout the surgery

General Anesthetics:

Can be administered as:

• Inhalational compounds (Halothane, Isoflurane, Enflurane)

• IV compounds (Barbiturates, Propofol, Ketamine, Opiates).

Are compounds that depress excitatory brain activity, accentuate inhibitory brain activity, or both.

Mechanisms of action:

Textbook Explanation:

“The exact mechanism by which inhalational anesthetics function is not known. There appears to be a correlation between anesthetic potency and lipid solubility (Meyer-Overton theory), suggesting that these anesthetics likely affect the lipid matrix of nerve cell membranes in the brain. Furthermore, NMR and electron spin resonance studies indicate that anesthetics cause a local disordering of the lipid membrane matrix, possibly decreasing the number of molecules that alternate simultaneously between the gel and crystalline states, and thereby altering membrane function”.

Inhalational Anesthetics

Halothane

Mechanisms of action:

Intravenous Anesthetics

Diverse mechanisms of action, depending on the drug (Benzodiazepines, Opiates, Propofol, etc…)Fentanyl KetamineDiazepam Propofol

However, they all affect

Synaptic Activity.