Introduction & layout of entries

Edward C. Conley

Entry 02 resumé

The Ion Channel FactsBook is intended to provide a ‘summary of molecular properties’ for all known types of ion channel protein in a cross-referenced and ‘computer-updatable’ format. Today, the subject of ion channel biology is an extraordinarily complex one, linking several disciplines and technologies, each adding its own contribution to the knowledge base. This diversity of approaches has left a need for accessible information sources, especially for those reading outside their own field. By presenting ‘facts’ within a systematic framework, the FactsBook aims to provide a ‘logical place to look’ for specific information when the need arises. For students and researchers entering the field, the weight of the existing literature, and the rate of new discoveries, makes it difficult to gain an overview. For these readers, The Ion Channel FactsBook is written as a directory, designed to identify similarities and differences between ion channel types, while being able to accommodate new types of data within the framework. The main advantages of a systematic format is that it can speed up identification of functional links between any ‘facts’ already in the database and maybe provide a raison d’être for specific experiments where information is not known. Although such ‘facts’ may not go out-of-date, interpretations based on them may change considerably in the light of additional, more direct evidence. This is particularly true for the explosion of new information that is occurring as a direct consequence of the molecular cloning of ion channel genes. It can be anticipated that many more ion channel genes will be cloned in the near future, and it is also likely that their functional diversity will continue to exceed expectations based on pharmacological or physiological criteria alone.

An emphasis on properties emergent from ion channel molecular functions

Understanding how the interplay of currents through many specific ion channel molecules determines complex electrophysiological behaviour of cells remains a significant scientific challenge. The approach of the FactsBook is to associate and relate this complex cell phenotypic behaviour (e.g. its physiology and pharmacology) to ion channel gene expression-control wherever possible even where the specific gene has not yet been cloned. Thus the ion channel molecule becomes the central organizer, and accordingly arbitrates whether information or topics are included, emphasized, sketched-over or excluded. In keeping with this, ion channel characteristics are described in relation to known structural or genetic features wherever possible (or where they are ultimately molecular characteristics). Invariably, this relies on the availability of sequence data for a given channel or group of channels. However, a number of channel types exist which have not yet been sequenced, or display characteristics in the native form which are not precisely matched by existing clones expressed in heterologous cells (or are otherwise ambiguously classified). To accommodate these channel types, summaries of characteristics are included in the standard entry field format, with inappropriate fieldnames omitted. Thus the present ‘working arrangement’ of entries and fields is broad enough to include both the ‘cloned’ and ‘uncloned’ channel types, but in due course will be gradually supplanted by a comprehensive classification based on gene locus, structure, and relatedness of primary sequences. In all cases, the scope of the FactsBook entries is limited to those proteins forming (or predicted to form) membrane-bound, integral ionic channels by folding and association of their primary protein sequences. Activation or suppression of the channel current by a specified ligand or voltage step is generally included as part of the channel description or name (see below). Thus an emphasis is made throughout the book on intrinsic features of channel molecule itself and not on those of separately encoded, co-expressed proteins. In the present edition, there is a bias towards descriptions of vertebrate ion channels as they express the full range of channel types which resemble characteristics found in most eukaryotes.

Anticipated development of the dataset – Integration of functional information around molecular types

Further understanding of complex cellular electrical and pharmacological behaviour will not come from a mere catalogue of protein properties alone. This book therefore begins a process of specific cross-referencing of molecular properties within a functional framework. This process can be extended to the interrelationships of ion channels and other classes of cell-signalling molecules and their functional properties. Retaining protein molecules (i.e. gene products) as ‘fundamental units of classification’ should also provide a framework for understanding complex physiological behaviour resulting from co-expressed sets of proteins. Significantly, many pathophysiological phenotypes can also be linked to selective molecular ‘dysfunction’ within this type of framework. Finally, the anticipated growth of raw sequence information from the human genome project may reveal hitherto unexpected classes and subtypes of cell-signalling components – in this case the task then will be to integrate these into what is already known (see also description of Field number 06: Subtype classifications and Field number 05: Gene family).

The Cell-Signalling Network (CSN)

From the foregoing discussion, it can be seen that establishment and consolidation of an integrated ‘consensus database’ for the many diverse classes of cell signalling molecules (including, for example, receptors, G proteins, ion channels, ion pumps, etc.) remains a worthwhile goal. Such a resource would provide a focus for identifying unresolved issues and may avoid unnecessary duplication of research effort. Work has begun on a prototype cell-signalling molecule database cooperatively maintained and supported by contributions from specialist groups: The Cell-Signalling Network (CSN) in mid-1996 has been designed to disseminate consensus properties of a wide range of molecules involved in cell signal transduction. While it will take some time (and much good-will) to establish a comprehensive network, the many advantages of such a co-operative structure are already apparent. Immediately, these include an ‘open’ mechanism for consolidation and verification of the dataset, so that it holds a ‘consensus’ or ‘validated’ set of information about what is known about each molecule and practical considerations such as nomenclature recommendations (see, for example, the IUPHAR nomenclature sections under the CSN ‘home page’).

The CSN also allows unlimited cross-referencing by pointing to related information sets, even where these are held in multiple centres. On-line descriptions of technical terms (glossary items, indicated by dagger symbols (†) throughout the text) and reference to explanatory references (e.g. on associated signalling components such as G protein†-linked receptors†) are being written for use with this book. Eventually, applications could include (for instance) direct ‘look-up’ of graphical resources for protein structure, in situ and developmental gene expression atlases†, interactive molecular models for structure/function analysis, DNA/protein sequences linked to feature tables, gene mapping resources and other pictorial data. These developments (not presently supported) will use interactive electronic media for efficient browsing and maintenance. For a brief account of the Cell-Signalling Network, see Feedback & CSN access, entry 12. For a full specification, see Resource J – Search criteria & CSN development.

HOW TO USE THE ION CHANNEL FACTSBOOK

Common formats within the entries

A proposed organizational hierarchy for information about ion channel molecules

Information on named channel types is grouped in entries under common headings which repeat in a fixed order – e.g. for ion channel molecules which have been sequenced, there are broad sections entitled NOMENCLATURES, EXPRESSION, SEQUENCE ANALYSES, STRUCTURE & FUNCTIONS, ELECTROPHYSIOLOGY, PHARMACOLOGY, INFORMATION RETRIEVAL and REFERENCES, in that order. Within each section, related fieldnames are listed, always in alphabetical order and indexed by a field number (see below), which makes electronic cross-referencing and ‘manual’ comparisons easier.

While the sections and fields are not rigid categories, an attempt has been made to remain consistent, so that corresponding information for two different channels can be looked up and...