Effect of parathyroid hormone on the connecting tubule from the rabbit kidney: biphasic response of transmural voltage

The effect of parathyroid hormone (PTH) on ion transport was examined by observing transmural (V _T) and basolateral membrane voltage (V _B) in the in vitro perfused rabbit connecting tubule. Addition of 10 nmol/l PTH to the bath induced a biphasic response of V _T, with hyperpolarization followed by depolarization. Chlorophenylthioadenosine cyclic 3,5-monophosphate mimicked the effect of PTH, which did not change the V _B in the connecting tubule cell, but mainly caused changes in the apical membrane voltage. The V _T of distal convoluted tubule and the cortical collecting duct were not affected by PTH. Elimination of Na⁺ from the lumen abolished the PTH-induced V _T responses in the connecting tubule. In the presence of 10 mol/l amiloride, PTH caused an initial hyperpolarization but did not induce the late depolarization. The same was seen in the absence of luminal Ca²⁺. Either addition of 0.1 mmol/l ouabain to the bath or elimination of bath Na⁺ completely abolished the PTH-induced V _T changes. The presence of 5 mmol/l Ba²⁺ in the lumen did not affect the response to PTH. These findings indicate that the initial hyperpolarization may be caused by an increase in Na⁺ influx across the luminal membrane through an amiloride-insensitive Na⁺ conductive pathway and that the late depolarization may be caused by the decrease in Na⁺ influx through the amiloride-sensitive Na⁺ conductive pathway. Luminal Ca²⁺ is necessary for the late depolarization caused by PTH. On the basis of these observations, we suggest that PTH initially increase influxes of both Na⁺ and Ca²⁺ across the luminal membrane and that an increase in intracellular Ca²⁺ in turn suppresses Na⁺ entry through the luminal amiloride-sensitive Na⁺ channel.