University of Massachusetts Medical School, Worcester

A molecular biologist considers the corollary of misbehaving ion channels

More than half a century ago, Hodgkin and Huxley hypothesized that pore-forming proteins found in a cell membrane could regulate the flow of ions across that membrane. These days, we classify ion channels according to the ions they allow through and the nature of the pore-forming protein. The crucial part of a pore is the protein's alpha subunit, which lines the pore. Auxiliary subunits, denoted by other letters of the Greek alphabet, merely tweak a channel's characteristics.

The basics infer an assumption: that different channels can interact with each other, but that subunits buried within a channel are 'married' to that channel 'for life'. A voltage-activated calcium channel can, for instance, form a pair with a large-conductance calcium-activated potassium channel. But a beta subunit of the calcium channel can associate only with the calcium channel's main alpha subunit, and a beta subunit of the potassium channel remains 'faithful' to the alpha subunit that surrounds the potassium pore.

However, assumptions should always be tested. In this case, Shengwei Zou and his colleagues at the University of Houston in Texas have taken the potassium channel in this example and shown that it is bound by an auxiliary beta-1 subunit of an L-type calcium channel (Cav1). When this subunit interacts with the potassium pore, it alters both the pore's kinetics and calcium sensitivity (S. Zou et al. Mol. Pharmacol. 73, 369–378; 2008).

I view this finding as part of an emerging theme, the ramifications of which could be profound. Ion channels may, in general, be much more dynamic structures than is currently recognized. This means that when researchers monitor a channel's activity they may not be recording exactly what they think they are — and that targeting ion channels with new drugs could produce unexpected side effects.