Multiple Sodium Channel Subtypes

The nine isoforms of sodium channels share a common overall structural motif but have different amino acid sequences (Catterall, 1992; Plummer and Meisler, 1999; Goldin et al., 2000). The functional characteristics of many of these channels have now been studied, and these analyses have demonstrated that different sodium channel isoforms can exhibit different voltage-dependences, activation and inactivation kinetics, and recovery properties. Some subtypes of sodium channels open, close, and reprime rapidly; others have slower kinetics; while still others can remain persistently open (see, for example, Dib-Hajj et al., 1997; Cummins et al., 1999, 2001; Herzog et al., 2003). Recent studies have also shown that the selective expression of different ensembles of sodium channels contributes to the different functional properties of different types of neurons. Threshold, refractory period, and the temporal patterning of action potentials are all influenced by the type(s) of sodium channels that are expressed within a given neuron (see, for example, Stuart and Sakmann, 1995; Pennartz et al., 1997; Waxman, 2000; Taddese and Bean, 2002). Thus, it is not unexpected that changes in sodium channel expression can have significant effects on neuronal function.

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