Channel nomenclature: IUPHAR recommendations

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TiPS - December 1993 [Vol. 14] 435 Potassium channel nomenclature: a personal view Potassium channels are ion chan- nels that are both ubiquitous and highly diverse. The diversity of voltage-gated K-channels is manifested biologically in distinct voltage-dependencies and kinetics of activation and inactivation, in distinct sensitivities for extra- cellular and intracellular ligands (e.g. K +, Ca 2+, Mg 2+, ATP, cAMP, G proteins) in distinct single chan- nel behaviours such as mean open durations and conductance, and in distinct ion selectivities. Vari- ations in any one of these proper- ties appears to lead to a bewilder- ing number of distinct K-channels, the properties of which have been described for both excitable and non-excitable cells. Remarkable progress has been made recently in the molecular biology of K-channels. This prog- ress has shed considerable light on the structural diversity of K- channels. Much has been learned about the structure of the proteins that form K-channels in in vitro expression systems, but determi- nation of the physiological roles of the cloned K-channel forming proteins is still a largely unsolved problem. Thus, it has to be realized that the presently existing no- menclature on cloned K-channel- forming proteins 1 is not, and cannot be, a nomenclature for K- channels; rather it is a unifying list of clone names, which may help to straighten out the Baby- lonian confusion on ion-channel cDNA clones, presently in use in many different laboratories. In this context, it is quite amusing to see that we have adopted one no- menclature for cloned human K- channel genes and another one for cloned K-channels encoded in non-human genomes. A nomencla- ture for endogenous K-channels has the burden of coping not only with the general diversity of K- channels, but also with the colt- fusion between K-currents and K- channels. Towards this end, it may be helpful to look over the fence to the nomenclature in other systems. A well worked out nomenclature that comes to mind is the one of enzymes. Enzymes are classified into main groups according to the general type of reaction that they catalyse. The main groups are divided into sub- groups on the basis of substrate specificity. These are. further divided into subgroups, e.g. based on ions and cofactors required for activity. Finally, a fourth number is added as a serial number. For example, EC 3.4.17.1 stands for: EC, enzyme commission; 3, hydrolases as main group; 4, peptidases as subgroup; 17, metal- carboxypeptidase as a further sub- group; 1, serial number. In my opinion, it would be very useful if the ion channel field could adopt a similar system. Although not everybody may agree with this, I can only empha- size that K-channels, like any other ion channels, are enzymes. After all, ion channels are integral membrane proteins that catalyse the flow of ions across the mem- brane. Therefore, I think that a discussion about K-channel no- menclature on one side and K-cur- rent nomenclature on the other, is superficial and detracts from the real issue. Such a discussion may be compared to a situation where one would argue about one nomenclature for enzymes and a separate one for reactions catalysed by enzymes. Thus, a future nomenclature should not attempt to refine or extend the present trivial ones. Here one should keep historical names in their own right, and not attempt to 'improve' them. If one takes enzyme nomencla- ture as a guideline, then one could start with ion channels in general. Main groups might specify which type of current the channel carries [e.g. cation (Na, Ca, K, H), anion (C1) or ionic (charged molecule) currents]. The first subgroup division might specify the chemical or physical agent that opens the channel (e.g. transmitter, ion, G protein, cyclic nucleotide or change in membrane potential). The second subgroup may refer to the Eisen- man ion selectivity series followed by a serial number. A less than ideal nomenclature may be one that attempts to sub- divide ion channels according to their mode of inactivation (e.g. delayed rectifier or A-type) or according to channel conductance properties (e.g. small K or large K). Using this nomenclature, enzymes would have been classified as allosteric or non-allosteric pro- teins, or as fast or slow catalysts. Finally, biochemists still often use trivial names for their enzymes, largely for historical and senti- mental reasons. Thus, it is to be expected that any systematic nomenclature on ion channels would not entirely substitute or eliminate trivial names that are currently in use. However, a systematic K-channel nomencla- ture is clearly important for refer- ence, and should be established. OLAF PONGS Zentrum fiir Molekulare Neurobiologie, Institut fiir Neurale Signalverarbeitung, Martinistra/~e 52, Haus 42, D-20246 Hamburg, Germany. Reference 1 Gutman, G. A. and Chandy, K. G. (1993~i Sere. Neurosci. 5, 101-106 Channel nomenclature: IUPHAR recommendations The International Union of Pharmacology (IUPHAR) created a nomenclature committee to standardize terms, initially for receptors, but also for cell mem- brane channels. The core com- mittee consists of molecular biologists, chemists and industrial and academic pharmacologists and has established links with the International Union of Bio- chemistry and Molecular Biology (IUBMB) and the associated en- zyme nomenclature committees. There are currently 17 subcom- mittees preparing recommendations on a range of receptor and ion channel systems and a technical subcommittee is preparing a gloss- ary of pharmacological terms and definitions. The calcium channel subcommittee has already issued its recommendations for no- menclature 1. The formation of subcom- mittees is based on two criteria: (~) 1993, Elsevier Science Publishers Ltd (UK) 0165-6147/93/$06.00 430 TiPS - December 1993 [Vol. 14] need and feasibility of producing suitable recommendations. There is a limit to the number of sub- committees that can be run effect- ively. We initially quailed before the task of classifying potassium channels on the grounds that the difficulties were enormous, and we had not yet established suf- ficient guidelines. Our relative success in other areas does now allow us to form a subcommittee and the fact that Drs Edwards, Weston, Chandy, Gutman and Pongs feel sufficiently motivated to write about the matter results in their being asked to be founding members, together with the further addition of chemists, molecular biologists, electrophysiologists and pharmacologists. An IUPHAR committee by definition represents the con- sensus view, but in other areas we have previously managed to marry function with genetics. It is to be hoped that such a marriage will lead to a workable scheme in the case of potassium channels. Because such consensus takes some time to establish, IUPHAR will not be able to contribute to the current debate but refers readers to previous committee nomenclature directives 2,3. Clear guidelines have been laid down as to how to classify chan- nels, using molecular b~ology, electrophysiological, biochemical and pharmacological criteria 1. These criteria are also applicable to potassium channels. Classifi- cations should not be based on just one experimental discipline. For example, Ii< obviously refers to potassium current, but in electro- physiology, this refers to the charge carrier and this well accepted convention should be adhered to. The pharmacology of Ica often differs markedly from IBa, even if the channel is the same. This is the reason why we did not promote Edward and Westons' idea of ICa(L); it may also be danger- ous for Ii