Dehydration increases L-type Ca(2+) current in rat supraoptic neurons.

The magnocellular neurosecretory cells of the hypothalamus (MNCs) regulate water balance by releasing vasopressin (VP) and oxytocin (OT) as a function of plasma osmolality. Release is determined largely by the rate and pattern of MNC firing, but sustained increases in osmolality also produce structural adaptations, such as cellular hypertrophy, that may be necessary for maintaining high levels of neuropeptide release. Since increases in Ca(2+) current could enhance exocytotic secretion, influence MNC firing patterns, and activate gene transcription and translation, we tested whether Ca(2+) currents in MNCs acutely isolated from the supraoptic nucleus (SON) of the hypothalamus are altered by 16-24 h of water deprivation. A comparison of whole-cell patch-clamp recordings demonstrated that dehydration causes a significant increase in the amplitude of current sensitive to the L-type Ca(2+) channel blocker nifedipine (from -56 +/- 6 to -99 +/- 10 pA; P < 0.001) with no apparent change in other components of Ca(2+) current. Post-recording immunocytochemical identification showed that this increase in current occurred in both OT- and VP-releasing MNCs. Radioligand binding studies of tissue from the SON showed there is also an increase in the density of binding sites for an L-type Ca(2+) channel ligand (from 51.5 +/- 4.8 to 68.1 +/- 4.1 fmol (mg protein)(-1); P < 0.05), suggesting that there was an increase in the number of L-type channels on the plasma membrane of the MNCs or some other cell type in the SON. There were no changes in the measured number of binding sites for an N-type Ca(2+) channel ligand. Dehydration was not associated with changes in the levels of mRNA coding for Ca(2+) channel alpha(1) subunits. These data are consistent with the hypothesis that a selective increase of L-type Ca(2+) current may contribute to the adaptation that occurs in the MNCs during dehydration.