title: A constitutively active nonselective cation conductance underlies resting Ca2+ influx and secretion in bovine adrenal chromaffin cells.
abstract: We have combined fluorimetric measurements of the intracellular free Ca(2+) concentration ([Ca(2+)](i)) with the patch clamp technique, to investigate resting Ca(2+) entry in bovine adrenal chromaffin cells. Perfusion with nominally Ca(2+)-free medium resulted in a rapid, reversible decrease in [Ca(2+)](i), indicating a resting Ca(2+) permeability across the plasma membrane. Simultaneous whole-cell voltage-clamp showed a resting inward current that increased when extracellular Ca(2+) (Ca(2+)(o)) was lowered. This current had a reversal potential of around 0 mV and was carried by monovalent or divalent cations. In Na(+)-free extracellular medium there was a reduction in current amplitude upon removal of Ca(2+)(o), indicating the current can carry Ca(2+). The current was constitutively active and not enhanced by agents that promote Ca(2+)-store depletion such as thapsigargin. Extracellular La(3+) abolished the resting current, reduced resting [Ca(2+)](i) and inhibited basal secretion. Abolishment of resting Ca(2+) influx depleted the inositol 1,4,5-trisphosphate-sensitive Ca(2+) store without affecting the caffeine-sensitive Ca(2+) store. The results indicate the presence of a constitutively active nonselective cation conductance, permeable to both monovalent and divalent cations, that can regulate [Ca(2+)](i), the repletion state of the intracellular Ca(2+) store and the secretory response in resting cells.
authors.affiliation: Institute for Cell and Molecular Biosciences, University of Newcastle-upon-Tyne, The Medical School, Framlington Place, Newcastle-upon-Tyne NE2 4HH, UK. t.r.cheek@ncl.ac.uk
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Cheek
authors.forename: Peter
authors.initials: P
authors.lastname: Thorn
mesh_terms: D000313:Adrenal Medulla / Q000166:cytology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002412:Cations; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism / Q000502:physiology*; D004553:Electric Conductivity; D005470:Fluorometry; D018408:Patch-Clamp Techniques; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D002412:Cations; D050051:Transient Receptor Potential Channels; D002118:Calcium