| Abstract No.: | 112 |
| Country: | Canada |
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| Title: | THE REGULATION OF ION CHANNELS IN SUPRAOPTIC NEURONS BY ACUTE AND CHRONIC CHANGES IN OSMOLALITY |
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| Authors/Affiliations: | 1 Thomas E. Fisher*;
1 University of Saskatchewan, Saskatoon, SK, Canada
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| Content: | The regulation of fluid balance in mammals depends on osmotically-evoked changes in the release of vasopressin (VP) from the magnocellular neurosecretory cells of the hypothalamus (MNCs). Increases in external osmolality cause the MNCs to fire action potentials more frequently due both to an increase in the firing of osmosensitive neurons that have excitatory inputs onto the MNCs and to an increase in responsiveness of the MNCs themselves. These effects depend on stretch inactivated cation currents that depolarize both types of cells in response to osmotically evoked cell shrinkage. Increases in osmolality also predispose the MNCs to firing in bursting patterns, but the mechanisms underlying this change are not well understood. Sustained increases in osmolality cause the MNCs to undergo reversible structural and functional changes, including cellular hypertrophy, an increase in certain cell surface receptors, and enhanced expression of several gene products. This transformation may be important in enabling the MNCs to sustain high levels of VP release. Objectives: We characterized the biophysical properties and functional role of a novel osmosensitive K+ current, which might contribute to the regulation of firing in the MNCs, and showed that prolonged water deprivation increases voltage gated Ca2+ currents, which may contribute to the adaptation of the MNCs to sustained increases in osmolality. Materials and Methods: We used whole cell patch clamp of acutely isolated MNCs to study the osmosensitive K+ current. We also used extracellular single unit recordings from hypothalamic explants to determine the effects of suppression and enhancement of this current on MNC firing. Ca2+ currents were evoked in MNCs isolated from either control rats or rats that had been deprived of water for 24 hours to determine how sustained dehydration affects Ca2+ currents. Results: Administration of a hypertonic external solution (325 mOsm) to isolated MNCs causes a rapid increase in a slow, TEA-insensitive K+ current. This current is selectively blocked by the M-channel blocker XE 991 and is potentiated by the M-channel opener retigabine. PCR and immunocytochemical evidence suggests that several members of the channel family that mediates M-currents are expressed in MNCs, including KV7.2, 7.3, 7.4, and 7.5. The administration of XE 991 to an explant preparation causes an increase in MNC firing, while administration of retigabine results in a slowing of firing. MNCs isolated from water deprived rats were found to have a specific elevation in nifedipine-sensitive L-type Ca2+ channels. This increase (about 77%) was not associated with an increase in mRNA coding for L-type channels. Conclusions: Both acute and longer term exposure to elevated osmolality appear to modulate the activity of specific voltage gated ion channels in MNC somata. Acute administration increases a slow K+ current that may influence MNC firing patterns, while longer administration results in a selective increase in L-type Ca2+ currents in MNC somata, which may contribute to the adaptation of the MNCs to sustained increases in osmolality. This work was supported by CIHR and the Saskatchewan Health Research Foundation. |
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