When Is a Potassium Channel Not a Potassium Channel?

Ever since they were first observed in Purkinje fibers of the heart, funny channels have had close connections to potassium channels. Indeed, funny channels were initially thought to produce a potassium current in the heart called . However, funny channels are completely unlike potassium channels in ways that make their contributions to the physiology of cells unique.

Altered cyclic nucleotide binding and pore opening in a diseased human HCN4 channel.

A growing number of nonsynonymous mutations in the human HCN4 channel gene, the major component of the funny channel of the sinoatrial node, are associated with disease but how they impact channel structure and function, and, thus, how they result in disease, is not clear for any of them. Here, we study the S672R mutation, in the cyclic nucleotide-binding domain of the channel, which has been associated with an inherited bradycardia in an Italian family. This may be the best studied of all known mutations, yet the underlying molecular and atomistic mechanisms remain unclear and controversial.

Regulation of sinoatrial funny channels by cyclic nucleotides: From adrenaline and I to direct binding of ligands to protein subunits.

The funny current, and the HCN channels that form it, are affected by the direct binding of cyclic nucleotides. Binding of these second messengers causes a depolarizing shift of the activation curve, which leads to greater availability of current at physiological membrane voltages. This review outlines a brief history on this regulation and provides some evidence that other cyclic nucleotides, especially cGMP, may be important for the regulation of the funny channel in the heart.

An ion channel in the company of a transporter.

In the current issue of , Lamothe and Kurata explore the functional relationship between the Kv1.2 potassium channel, with Kvβ1.2 bound to the interior aspect of the channel, and Slc7a5, a component of the neutral amino acid transporter LAT1.