Physiological Reviews, Vol 76, 887-926, Copyright © 1996 by American Physiological Society
Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms
H. A. Fozzard and D. A. Hanck
Department of Pharmacological and Physiological Sciences, The University of Chicago, Illinois, USA.
Cardiac and nerve Na channels have broadly similar functional properties
and amino acid sequences, but they demonstrate specific differences in
gating, permeation, ionic block, modulation, and pharmacology. Resolution
of three-dimensional structures of Na channels is unlikely in the near
future, but a number of amino acid sequences from a variety of species and
isoforms are known so that channel differences can be exploited to gain
insight into the relationship of structure to function. The combination of
molecular biology to create chimeras and channels with point mutations and
high-resolution electrophysiological techniques to study function encourage
the idea that predictions of structure from function are possible. With the
goal of understanding the special properties of the cardiac Na channel,
this review examines the structural (sequence) similarities between the
cardiac and nerve channels and considers what is known about the
relationship of structure to function for voltage-dependent Na channels in
general and for the cardiac Na channels in particular.
