STRUCTURAL BASIS OF POTASSIUM CHANNEL DIVERSITY IN THE NERVOUS SYSTEM

A variety of voltage-sensitive potassium channels has been described which differ in their electrophysiological and pharmacological properties. Potassium channels which mediate outward K+ currents in response to changes in membrane polarisation differ most notably in their voltage sensitivity and their opening and closing kinetics, as well as their recovery times from inactivation. Also, some of these potassium channels are sensitive to toxins like dendrotoxin and mast cell degranulating peptide; others are not. We have cloned and sequenced a variety of cDNAs encoding potassium channel subunits present in invertebrate as well as vertebrate central nervous systems. Injection into Xenopus oocytes of RNA synthesized in vitro using the various cDNAs as a template results in the expression of functional potassium channels. Some of these channels exhibit properties similar to those of the non-inactivating delayed rectifier channel found in many excitable cells, yet differ in their sensitivities towards potassium channel blocking agents. The properties of other channels expressed from cRNA injected into Xenopus oocytes resemble those of transient A-type channels which inactivate rapidly after opening upon membrane depolarisation. A comparison of the derived primary sequences of the different potassium channels allows a direct correlation of channel protein structures with electrophysiological and pharmacological properties, respectively.