Linked Life Data

16962713

Source:http://linkedlifedata.com/resource/pubmed/id/16962713

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-11-19
pubmed:abstractText
Chromaffin cells of the adrenal medulla represent a primary output of the sympathetic nervous system. Their electrical stimulation evokes the fusion of large dense core granules with the cell membrane and the exocytic release of multiple transmitter molecules into the circulation. There the transmitters contribute to the regulation of basic metabolism of the organism. Under physiological activity, granule fusion and transmitter release are limited by activity-dependent Ca(2+) influx, entering through multiple isoforms of voltage-gated calcium channels. In this study we utilize perforated-patch voltage-clamp recordings and depolarize mouse chromaffin cells in situ with action potential-like waveforms to mimic physiological firing. We measure calcium influx through specific isoforms and measure cell capacitance as an index of granule fusion. Combining these approaches we calculate specific stimulus-secretion efficiencies for L-type, N-type, P/Q-type and R-type calcium channels under varied physiological activity levels. Current influx through all channel subtypes exhibited an activity-dependent depression. As expected P/Q-type channels, while responsible for modest Ca(2+) influx, are tightly coupled to catecholamine secretion under all conditions. We further find that stimulation designed to match sympathetic input under the acute stress response recruits L-type channels to a state of enhanced stimulus-secretion efficiency. N- and R-type channels do not undergo activity-dependent recruitment and remain loosely coupled to the secretion. Thus, only L-type channels exhibit activity-dependent changes in their stimulus-secretion function under physiological stimulation. Lastly, we show that treatment with the beta-adrenergic agonist, isoproterenol, specifically blocks the increase in the stimulus-secretion function of L-type channels. Thus, increased cell firing specifically enhances stimulus-secretion coupling of L-type Ca(2+) channels in chromaffin cells in situ. This mechanism is regulated by an adrenergic signaling pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
445-59
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:16962713-Action Potentials, pubmed-meshheading:16962713-Adrenal Medulla, pubmed-meshheading:16962713-Adrenergic beta-Agonists, pubmed-meshheading:16962713-Animals, pubmed-meshheading:16962713-Cadmium Chloride, pubmed-meshheading:16962713-Calcium, pubmed-meshheading:16962713-Calcium Channel Blockers, pubmed-meshheading:16962713-Calcium Channels, L-Type, pubmed-meshheading:16962713-Calcium Signaling, pubmed-meshheading:16962713-Chromaffin Cells, pubmed-meshheading:16962713-Dose-Response Relationship, Radiation, pubmed-meshheading:16962713-Drug Interactions, pubmed-meshheading:16962713-Electric Stimulation, pubmed-meshheading:16962713-Epinephrine, pubmed-meshheading:16962713-Exocytosis, pubmed-meshheading:16962713-Isoproterenol, pubmed-meshheading:16962713-Mice, pubmed-meshheading:16962713-Mice, Inbred C57BL, pubmed-meshheading:16962713-Microscopy, Electron, Transmission, pubmed-meshheading:16962713-Patch-Clamp Techniques, pubmed-meshheading:16962713-Signal Transduction
pubmed:year
2006
pubmed:articleTitle
An activity-dependent increased role for L-type calcium channels in exocytosis is regulated by adrenergic signaling in chromaffin cells.
pubmed:affiliation
Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural