Date of Award:

5-1-2000

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Biology

Committee Chair(s)

Peter Ruben

Committee

Peter Ruben

Committee

Daryll DeWald

Committee

Jon Takemoto

Abstract

Ionic currents flowing through voltage-gated sodium (Na+) channels generate the rising phase of action potentials. This process is essential for normal cellular excitability and it is important to investigate the structure/function relationships that allow Na+ channels to change conformations in response to membrane potential. The Na+ channel skeletal muscle (SkM) α subunit is made of four homologous domains (DI-IV), with six transmembrane segments (S1-6) in each domain. One transmembrane segment in the channel, segment four in domain four (DIVS4), appears to make critical contributions to several aspects of channel activity. In this study, wild type (WT) and charge-neutralized rat SkM Na+ channel α subunits were coexpressed with the rat β1 subunit in Xenopus oocytes. Channel neutralizations consisted of single arginine (R) to glutamine (Q) substitutions for the fourth through the seventh charged residues (R1450Q, R1453Q, R1456Q, and R1459Q, respectively) in DIVS4. Channel activity was characterized using cell-attached macropatches. The charge neutralizations were found to affect activation, deactivation, fast inactivation, and slow inactivation. In addition, the data suggest that DIVS4 charges: 1) contribute to coupling fast inactivation to activation and 2) are involved in the inhibitory relationship between fast and slow inactivation.

Download

Included in

Biology Commons

Share

COinS

Copyright for this work is retained by the student. If you have any questions regarding the inclusion of this work in the Digital Commons, please email us at .