STRUCTURE AND FUNCTION OF VOLTAGE-DEPENDENT SODIUM-CHANNELS - COMPARISON OF BRAIN-II AND CARDIAC ISOFORMS

Cardiac and nerve Na channels have broadly similar functional properti es and amino acid sequences, but they demonstrate specific differences in gating, permeation, ionic block, modulation, and pharmacology. Res olution of three-dimensional structures of Na channels is unlikely in the near future, but a number of amino acid sequences from a variety o f species and isoforms are known so that channel differences can be ex ploited 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 techniq ues to study function encourage the idea that predictions of structure from function are possible. With the goal of understanding the specia l properties of the cardiac Na channel, this review examines the struc tural (sequence) similarities between the cardiac and nerve channels a nd considers what is known about the relationship of structure to func tion for voltage-dependent Na channels in general and for the cardiac Na channels in particular.