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Pharmacology of Voltage-Gated K+Channels

  • Chapter
Potassium Channels in Cardiovascular Biology

Abstract

To completely describe the pharmacology of voltage-gated K+ channels would take an entire volume, and that volume would probably be obsolete before it appeared on bookshelves. This chapter is therefore necessarily a restricted view. Many excellent reviews of K+ channel pharmacology are available (e.g., Chandy and Gutman, 1995; Fedida, et al., 1998; see elsewhere in this volume). Here, we focus on pharmacology of cloned voltage-gated (Kv) subunits known to be important in cardiac function. Since we now know the molecular targets of many drugs, and in some cases even which regions of the channel protein are necessary for drug action, this chapter deals mainly with results obtained from electrophysiological experiments using expression systems, in which the experimenter can focus on a single, identified channel. Using molecular biological techniques, such as Northern blotting or antibody labeling to determine what channels are present in heart tissues, it is relatively simple to put the cDNA or cRNA for this channel subunit in an expression system and examine its pharmacology. Such approaches to understanding pharmacology have great advantages over approaches that employ isolated myocytes, where one has to use often complex procedures (voltage protocols, blocking agents) to dissect out the K+ current of interest. The molecular/ electrophysiological approach of studying K+ channels in expression systems has been tremendously successful, as several examples cited here will hopefully show. However, there are potential drawbacks; for instance, in vivo, Kv channels probably assemble as heteromultimers, comprised of a mixture of α-subunits and perhaps other subunits, complicating their pharmacology; different expression systems may give different results, for a variety of technical reasons; The IC50 values which one has worked so hard to obtain for a particular compound may have little relation to therapeutically relevant concentrations in the working (human) heart at 37°C.

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Authors and Affiliations

  1. Electrophysiology Group, Department of Biochemistry, Imperial College of Science, Medicine & Technology, London, SW7 2AY, UK

    Brian Robertson

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  1. Walter McKenzie Health Science Centre, University of Alberta Hospital, Edmonton, Alberta, Canada

    Stephen L. Archer

  2. Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Nancy J. Rusch

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Robertson, B. (2001). Pharmacology of Voltage-Gated K+Channels. In: Archer, S.L., Rusch, N.J. (eds) Potassium Channels in Cardiovascular Biology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1303-2_12

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  • DOI: https://doi.org/10.1007/978-1-4615-1303-2_12

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