The Molecular Basis of Chloride Transport in Shark Rectal Gland

Journal of Experimental Biology - Tập 196 Số 1 - Trang 405-418 - 1994
John R. Riordan1, Bliss Forbush1, John W. Hanrahan1
1The Hospital for Sick Children, Toronto, Ontario, Canada

Tóm tắt

ABSTRACT

Transepithelial Cl− secretion in vertebrates is accomplished by a secondary active transport process brought about by the coordinated activity of apical and basolateral transport proteins. The principal basolateral components are the Na+/K+-ATPase pump, the Na+/K+/2Cl− cotransporter (symporter) and a K+ channel. The rate-limiting apical component is a cyclic-AMP-stimulated Cl− channel. As postulated nearly two decades ago, the net Cl− movement from the blood to the lumen involves entry into the epithelial cells with Na+ and K+, followed by active Na+ extrusion via the pump and passive K+ exit via a channel. Intracellular [Cl−] is raised above electrochemical equilibrium and exits into the lumen when the apical Cl− channel opens. Cl− secretion is accompanied by a passive paracellular flow of Na+. The tubules of the rectal glands of elasmobranchs are highly specialized for secreting concentrated NaCl by this mechanism and hence have served as an excellent experimental model in which to characterize the individual steps by electrophysiological and ion flux measurements. The recent molecular cloning and heterologous expression of the apical Cl− channel and basolateral cotransporter have enabled more detailed analyses of the mechanisms and their regulation. Not surprisingly, since hormones acting through kinases control secretion, both the Cl− channel, which is the shark counterpart of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), and the cotransporter are regulated by phosphorylation and dephosphorylation. The primary stimulation of secretion by hormones employing cyclic AMP as second messenger activates CFTR via the direct action of protein kinase A (PKA), which phosphorylates multiple sites on the R domain. In contrast, phosphorylation of the cotransporter by as yet unidentified kinases is apparently secondary to the decrease in intracellular chloride concentration caused by anion exit through CFTR.

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