5_IonChannels-PreLab - BIO 335 WEEK 5 ION CHANNELS I....

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BIO 335 WEEK 5 ION CHANNELS I. OBJECTIVES 1. Expand understanding of physiology of ion channels. 2. Learn basic concepts of voltage-clamping. 3. Understand current-voltage relationships. 4. Understand the relationship between microscopic (single channel) and macroscopic currents. 5. Understand how ion channels are stochastic. 6. Begin to understand the structure/function of ion channels. Overall Goal : Learn how transmembrane proteins—voltage-gated ion channels—regulate membrane excitability at a molecular and kinetic level. II. BACKGROUND In 1952, Alan Hodgkin and Andrew Huxley published a set of manuscripts (in the Journal of Physiology) that described mechanisms regulating membrane excitability—specifically the action potential. This work may seem ancient to us now but at the time it was so novel and groundbreaking that no significant advances in the field occurred until more than ten years later. Many of the concepts Hodgkin and Huxley developed still remain in use today despite many technical advances—researchers studying the membrane properties of neurons still talk about Hodgkin-Huxley action potentials and describe them quantitatively using approaches developed in this work. Alan Hodgkin and Andrew Huxley, along with another great physiologist John Eccles, won the Noble Prize in Physiology and Medicine in 1963 and were later knighted by the Queen. We should all now be familiar with the general form of an action potential—the rising phase is due to the opening of voltage-gated Na + -channels and the decaying phase is due to inactivation or closing of these voltage-gated Na + channels and an opening (which is delayed relative to the Na + - channels) of voltage-gated K + channels. When Hodgkin and Huxley published their work, they did not talk about ‘ion channels’ but rather changes in membrane conductance or permeability without any clear definition as to how these arose (the rising phase is due to an increase in Na + conductance and the decaying phase an increase in K + conductance). Hodgkin and Huxley did propose a number of possible explanations for these changes in membrane conductance—e.g., the lipid bilayer might change its polarity allowing Na + and K + to cross the membrane differentially. We now know that these changes in membrane conductances or permeability are due to ’ion channels’, transmembrane proteins with a water-filled pore. During the 1960s and 1970s, many scientists developed the concept of ‘ion channels’—that changes in membrane permeability were due to specific molecular entities (championed by Clay Armstrong and Bertil Hille among others). Although the evidence was overwhelming positive, the ‘concept’ of ion channels was fully verified
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This note was uploaded on 12/06/2011 for the course BIO 335 taught by Professor Cabot during the Fall '08 term at SUNY Stony Brook.

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5_IonChannels-PreLab - BIO 335 WEEK 5 ION CHANNELS I....

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