Intracellular calcium in the transmission of tubuloglomerular feedback signals

Abstract

Macula densa cytoplasmic Ca may serve in the transmission of feedback signals. This was based, in part, on the finding that the calcium ionophore A23187 [calcimycin] in the presence of perfusate calcium enhanced the feedback responses obtained with a 70 mosmol/kg hypotonic solution. The role of Ca was evaluated in the transmission of feedback signals and, in particular, to determine the source for the increase in cytosolic Ca during feedback responses. Stop-flow pressure (SFP) feedback responses were evaluated in rats during retrograde microperfusion from an early distal tubular site at 15 nl/min. During retrograde perfusion with an isotonic Ringer solution, alterations in perfusate Ca concentration (from 4 to 0 mEq/l) or addition of 10-3 M verapamil did not change the magnitude of the SFP feedback responses, which averaged between 12-13 mmHg. After 5 min of perfusion with the isotonic Ringer solution containing 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8), a putative inhibitor of intracellular release of bound Ca, SFP feedback responses were reduced by 57 .+-. 7% at 100 .mu.M TMB-8, 80 .+-. 5% at 300 .mu.M TMB-8, and 76 .+-. 6% at 500 .mu.M TMB-8. The addition of 5 .mu.M A23187 to the 500 .mu.M TMB-8 solution restored feedback responses to control values. Ca may be involved in the transmission of tubuloglomerular feedback signals. The source for the increase in cytosolic Ca during the transmission of feedback signals may be mobilization of Ca from bound or sequestered stores.