REGULATION OF APICAL NA+ CONDUCTIVE TRANSPORT IN EPITHELIA BY PH

Alterations in extracellular (pH(o)) and/or intracellular pH (pH(i)) have significant effects on the apical Na+ conductive transport in tight epithelia. They influence apical membrane Na+ conductance via a direct effect on amiloride-sensitive apical Na+ channel activity and indirectly through effects on the basolateral Na+/K+-ATPase. Changes in pH also modulate the hormonal regulation of apical Naf conductive transport. The pH sensitive steps in hormone action include: (i) hormone-receptor binding, (ii) increase in intracellular cyclic 3',5'-adenosine monophosphate (cAMP), (iii) mobilization of intracellular free Ca2+ ([Ca2+](i)), and (iv) incorporation of new channels into the apical membrane or recruitment of existing channels. Alternately, changes in pH induce secondary effects via alterations in [Ca2+](i). A reciprocal relationship between pH(i) and [Ca2+](i) has been demonstrated in renal epithelial cells. Natriferic hormones induce a significant increase in pH(i). There is a strong temporal relation between hormone-induced increase in pH(i) and overall increase in transepithelial Na+ transport. This suggests that changes in pH(i) act as an intermediate in the second messenger cascade initiated by the hormones. Several natriferic hormones activate Na+-H+ exchanger, H+-ATPase, H+/K+-ATPase, Hf conductive pathways in cell membranes or potential-induced changes in pH(i). However, changes in pH(i) do not seem to be essential for the hormone effect on Na+ conductive transport. It is suggested that the role of pH(i) changes during hormone action is permissive rather than strictly obligatory.