K-Cl cotransport systems

Abstract

The KCl cotransporter in the basolateral membrane of renal tubules may play a central role in the transcellular transport of NaCl. Because this transporter is electrically neutral, and also functions in parallel to the electrogenic Na,K-ATPase, there is an imbalance in charge which must be expressed as a cationic current across the basolateral membrane. Therefore, other pathways must also function in the basolateral membrane which permit the conductive exit of K+ in addition to the electrically-neutral KCl cotransporter. Another functional role for the KCl cotransporter is manifest during the cell volume regulatory response to cell swelling. In this setting (regulatory volume decrease), it appears that both electrically-neutral and electrically-coupled KCl efflux pathways are acutely activated. Very little is known at present about the mechanisms of short and long term regulation of the KCl cotransporter. A major obstacle at this point is the lack of a suitable, potent (that is, microM range) specific inhibitor of this transporter. It also appears that the chloride transport systems in basolateral membrane vesicles may be greatly influenced by the precise details of the method of preparation. Once these experimental details are mastered, and a suitable high affinity inhibitor is identified, then the detailed characterization and identification of the KCl cotransporter can be undertaken.