Introduction to Neurochemistry I

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

VGNaC found only on the nodes Potassium leak channels present throughout neuron Voltage Gated K channels also in area around node

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)

Role of S4 helix in gating http://wilkes-fs1.wilkes.edu/~terzaghi/BIO-226/lectures/13.html

Activation of sodium channel through S4 movement (M-gate) Outside depol Cytosol Ready state: No Na entry (Vm=-70 mV) time Active State: Na enters (Vm=threshold)

H-gate inactivates sodium channel once Vm cytosol becomes positive Inactive Ready Active Na+ H-gate M-gate Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

Introduction to Neurochemistry I