Introduction to Neurochemistry I

Presentation by Josh Morrison for Biochemistry II

February 21, 2005

The Membrane Potential

• Vm is the symbol for Membrane Potential

• Vm is the electrical charge of a cell

• Present in all cells

Importance of Vm

• Source of potential energy for transporting ions and molecules across cell membrane i.e. Na/glucose cotransporter

• Determines if ion will be actively or passively transported across membrane

• Thus, to some extent, determines how cell will spend energy

Origin of Vm

• Vm is complex interaction between ion concentrations and the channels and pumps through which ions enter and exit cell

• To help understand the factors involved, let us look at a simple cell with only one positive and one negative ion

Simple Cell

• Recall physics. For electricity to exist, there must be a complete pathway for electron flow.

• Ion=charged particle (like electron). Thus, flow of ions equals electric flow.

Simple cell con’t

• Let’s say that the positive ion flows through channel from high concentration to low concentration (selective permeability)

• However, flow of charged particle causes electrical charge of cell to shift (from neutral to positive)

• Shift in electrical properties of cell disfavors flow of positive charge out of cell

Flow of ions in simple cell

Lecture #2 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

Nernst Equation

Eion=(RT)/(zF) log [ion]o / [ion]i

Or

Eion=58/charge log [ion]o / [ion]i

Nernst Equation

• Predicts Vm value for cell whose membrane is permeable to one ion

• Example calculation for K+

EK= 58/+1 log [5mM] / [125mM] = -81 mV

• Limits of Nernst

Wrap Up of Vm

• Real cells are permeable to many different ions

• Membrane’s permeability to ions major factor in determining what Vm (illustrated by Goldman-Hodgkin-Katz Eq.)

• Thus, the most conductant ion will have the greatest effect on Vm

Resting Potential

Lecture #2 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

Spike Initiation Zone

Myelin is actually Schwann cell wrapped around axon multiple times

The Action Potential

Action Potentials

• Mode of Communication in Neurons

• Intensity (frequency) determines magnitude of response

• Initiation-Propagation-Termination

Initiation

• Occurs only in SIZ

• Initially, only leak channels open (K+)

• Slight depolarization to threshold opens Voltage-gated Na channels (VGNaC)

• Na flows with electrochemical gradient, causing further depolarization

• All-or-none response

Action potential initiation

S.I.Z.

Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

Propagation

• Local Circuit Currents—Na diffuses down axon and depolarizes other places in axon

• AP Initiate in these nearby areas

• Saltatory conduction of AP due to myelin

Propagation

Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

Voltage Gated K channels also in area around node

Potassium leak channels present throughout neuron

VGNaC found only on the nodes

Termination

• VGNaC inactivate—cause repolarization

• At the same time, the depolarization has cause VGKC to open—speed repol

• Flow of K out of cell causes hyperpolarization

• Refractory Period—prevents “backwards” movement of AP

Action potential termination

Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

Ig loop (H-gate)

http://wilkes-fs1.wilkes.edu/~terzaghi/BIO-226/lectures/13.html

Role of S4 helix in gating

Activation of sodium channel through S4 movement (M-gate)

Outside

Cytosol

Ready state: No Na entry

(Vm=-70 mV)

Active State: Na enters

(Vm=threshold)

depol

time

H-gate inactivates sodium channel once Vm cytosol becomes positive

Ready InactiveActive

H-gateM-gate

Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

Na+