Dehydration increases L-type calcium channel density in the somata of magnocellular neurosecretory cells in rats
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The magnocellular neurosecretory cells (MNCs) of the hypothalamus are responsible for the synthesis and secretion of vasopressin (VP), which is important for fluid homeostasis, and oxytocin (OT), which is responsible for uterine contraction during parturition and milk let-down during lactation. VP-ergic MNCs undergo a number of structural and functional changes during dehydration, including the adoption of a bursting pattern of firing, the retraction of glial processes from MNC somata and terminals, the translocation of kappa-opioid receptors from internal stores to the plasma membrane, and the somatodendritic release of VP and OT. Since voltage-gated Ca2+ channels have been found on intracellular granules, and since an increase in Ca2+ current could regulate firing patterns and neuropeptide release, the surface expression of Ca2+ channel subtypes in MNCs was tested to determine if it would be altered by 16-24 hours of water deprivation. Using radioligand binding of antagonists of N-type and L-type Ca2+ channels, channel density was measured in the supraoptic nucleus (SON), which is largely composed of MNC somata, and in the neurohypophysis (NH), which is largely composed of MNC terminals. Dehydration caused an increase in the density of L-type channels in the SON, while causing no significant change in the N-type density. No change in density of either channel type was observed in the NH. Electrophysiological measurements in isolated MNC somata showed no change in total Ca2+ current, but a significant increase in the nifedipine-sensitive current following dehydration. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated no increase in messenger RNA levels for L-type channels, suggesting that the increase in channel density is not a consequence of de novo synthesis. These results suggest that L-type Ca2+ channels may be translocated from internal stores to the plasma membrane of MNCs in response to dehydration. Such a process may be important in maximizing secretion of VP when the physiological need is high.
DegreeMaster of Science (M.Sc.)
SupervisorFisher, Thomas E.
CommitteeWalz, Wolfgang; Tuchek, John M.; Sulakhe, Prakash; Desautels, Michel
Copyright DateJuly 2005
magnocellular neurosecretory cells