Basolateral [Mg.sup.2+]/[Na.sup.+] exchange regulates apical nonselective cation channel in sheep rumen epithelium via cytosolic [Mg.sup.2+]

High potassium diets lead to an inverse regulation of sodium and magnesium absorption in ruminants, suggesting some form of cross talk. Previous Ussing chamber experiments have demonstrated a divalent sensitive [Na.sup.+] conductance in the apical membrane of ruminal epithelium. Using patch-clamped ruminal epithelial cells, we could observe a divalent sensitive, nonselective cation conductance (NSCC) with [K.sup.+] permeability > [Cs.sup.+] permeability > [Na.sup.+] permeability. Conductance increased and rectification decreased when either [Mg.sup.2+] or both [Ca.sup.2+] and [Mg.sup.2+] were removed from the internal or external solution or both. The conductance could be blocked by [Ba.sup.2+], but not by tetraethylammonium (TEA). Subsequently, we studied this conductance measured as short-circuit current ([I.sub.sc]) in Ussing chambers. Forskolin, IBMX, and theophylline are known to block both [I.sub.sc] and Na transport across ruminal epithelium in the presence of divalent cations. When the NSCC was stimulated by removing mucosal calcium, an initial decrease in [I.sub.sc] was followed by a subsequent increase. The cAMP-mediated increase in [I.sub.sc] was reduced by low serosal [Na.sup.+] and serosal addition of imipramine or serosal amilofide and depended on the availability of mucosal magnesium. Luminal amiloride had no effect. Flux studies showed that low serosal [Na.sup.+] reduced [sup.28]Mg fluxes from mucosal to serosal. The data suggest that cAMP stimulates basolateral [Na.sup.+]/[Mg.sup.2+] exchange, reducing cytosolic Mg. This increases sodium uptake through a magnesium-sensitive NSCC in the apical membrane. Likewise, the reduction in magnesium uptake that follows ingestion of high potassium fodder may facilitate sodium absorption, as observed in studies of ruminal osmoregulation. Possibly, grass tetany (hypomagnesemia) is a side effect of this useful mechanism. magnesium transport; nonselective cation channel; sodium absorption; rumen