Ion channel modulators: more diversity than previously thought

Ion channel function can be modified in various ways. For example, numerous studies have shown that currents through voltage-gated ion channels are affected by pore block or modification of voltage-dependence of activation/inactivation. Recent experiments performed on various ion channels show that allosteric modulation is an important mechanism to affect channel function. For instance, in KCa2 (formerly SK) channels, the prototypic “blocker” apamin prevents conduction by an allosteric mechanism, while TRPV1 channels are prevented from closing by a tarantula toxin, DkTx, through an interaction with residues located away from the selectivity filter. The recent evidence therefore suggests that, in several ion channels, the region around the outer mouth of the pore is rich in binding sites which may be exploited therapeutically. These discoveries also suggest that the pharmacological vocabulary should be adapted to define these various actions.