The outwardly rectifying chloride channel is found in most vertebrate cells however its physiological role is uncertain. Patch clamp, short-circuit current, and electronic cell sizing techniques were used to investigate the role of the outward rectifier in transepithelial chloride secretion and cell volume regulation, the two main functions that have been proposed for this channel in epithelia. Patch clamp studies of the human cell lines PANC-1 and T$ sb{84}$ showed that the chloride channel blockers IAA-94 and NPPB decrease the open probability of the outward rectifier, with half-maximal inhibition at 15 $ mu$M and 23 $ mu$M, respectively. At these concentrations the blockers did not affect cAMP-induced short-circuit current. They did inhibit the regulatory volume decrease (RVD) which occurs after hypotonic cell swelling, but only at much higher concentrations. Moreover, the commonly-used inhibitor DIDS, which blocks the outward rectifier in the 10-20 $ mu$M range, had no effect on the RVD when tested at 100 $ mu$M. The results indicate that the outwardly rectifying Cl channel does not mediate a significant fraction of transepithelial Cl secretion across T$ sb{84}$ cells. Although the data do not exclude a role for the outward rectifier in cell volume regulation, the selectivity and pharmacological properties of the swelling-induced anion conductance in T$ sb{84}$ cells is more similar to the ClC-2 channel than to the outward rectifier.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68206 |
| Date | January 1993 |
| Creators | Low, Wendy |
| Contributors | Hanrahan, J. W. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001397497, proquestno: AAIMM94464, Theses scanned by UMI/ProQuest. |
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