Cellular Neurobiology Lecture 3

Learning Objectives

1) Describe how historical findings advanced our understanding of the nervous system, especially evidence supporting or refuting major hypothesis.

• Galvani vs Volta

  • Galvani - electrical stimulated frog muscles to contract > animal electricity

  • Volta - dissimilar metals used for stimulation muscle contraction > voltaic pile (battery)

  • Tissue respond to electrical charge (both)

• Refining hypothesis

  • Ion specific channels dictate electrical signaling

2) Describe neurobiological mechanisms related to topics of current interest discussed in class.

3) Describe how Hodgkin and Katz (1949) used the squid giant axon to test Bernstein’s first hypothesis (on the resting potential)

• Bernstein hypothesized that resting membrane potential was primarily due to the membrane’s permeability to K+ potassium

• H & K used squid giant axon

  • Recording electrode inside axon

  • Recorded transmembrane potential via altering K+ concentrations

  • RESULTS: RP shifted in a way that closely matched the predictions of Nernst equation for K+

  • RESULTS: Confirmed Bernstein’s hypothesis on K+ is primary ion for RP

4) Compare the results of Cole and Curtis (1939) vs Hodgkin and Huxley (1939) when each tested Bernstein’s second hypothesis (on the action potential). How did each support, or not support, the hypothesis?

• Bernstein hypothesized that an AP caused by general non specific increase in membrane permeability which would simply cause the membrane potential to break down towards 0mV

• C & C

  • Measured membrane conductance during AP

  • RESULTS: Found massive increase in conductance

  • Supported hypothesis > Membranes permeability increased during AP

• H & H

  • Recorded transmembrane AP

  • RESULTS: membrane potential dropped down towards 0mv AND kept going into the positives (+40mV)

  • Refuted hypothesis > proving that AP is not a generalized breakdown into a neutral state

5) Describe how Hodgkin’s insight (hypothesis) on the sequence of permeability changes could explain how the actional potential is produced?

• Overshot 0mV into positive

• Hypothesis: Specific sequence of permeability changes rather than general breakdown

  • Rising phase of AP caused by massive increase in sodium permeability (Pna » Pk)

    • Caused Na ions rush into cells and drive voltage up

  • Following, Na permeability decreases while K permeability becomes dominant again (Pk » Pna)

    • Caused K ions exit the cell repolarizing the membrane back to RP

Vocabulary

• Voltage - Driving force of flow of electricity, similar to pressure of water in tank

• Current - Actual flow of electricity, similar to flow of water through pipe

• Charge (q) - Amount of electricity present

• Resistance - Measures how much material restricts flow of electricity

• Conductance - Measures how well material allows electricity flow

• Ion Transporters - Active membrane proteins that move ions against their gradients (like the NaK transporters pumping K in and Na out)

• Ion Channels - Membrane proteins that provide a pore for specific ions to flow passively into or out of the cell based on their gradients

• Nernst Equation - Formula to calculate the specific equilibrium potential fora single individual ion

• Goldman Equation - A broad formula used to calculate the overall membrane potential by factoring in the relative permeabilities of multiple active ions

• Voltage Clamp - An expt. apparatus that allows researchers to clamp (hold constant ) the membrane voltage at a desired level in order to accurately measure the underlying ionic currents