Linked Life Data

12080097

Source:http://linkedlifedata.com/resource/pubmed/id/12080097

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-6-24
pubmed:abstractText
We previously demonstrated that activation of a 5HT(4) receptor coupled cAMP-dependent signaling pathway increases tetrodotoxin-resistant Na(+) current (I(Na)) in a nociceptor-like subpopulation of rat dorsal root ganglion cells (type 2). In the present study we used electrophysiology experiments and computer modeling studies to explore the mechanism(s) underlying the increase of I(Na) by 5HT. In electrophysiological experiments with type 2 dorsal root ganglion cells, 5HT increased peak I(Na) and the activation and inactivation rate, without significantly affecting the voltage dependency of activation or availability. Studies on the voltage dependency of channel availability, time course of removal of inactivation, and inactivation of evoked Na(+) currents suggested that there are at least two inactivation states of the Na(+) channel, one (I(fast)) that is induced and retrieved faster than the other (I(slow)). Long (1 s), but not short (60 or 100 ms), inactivating conditioning pulses (CPs) suppressed the 5HT-induced increase in I(Na). Computer modeling studies suggest that 5HT increased I(Na) mainly by decreasing the transition rate (k(OI1)) from an open state to I(fast). Furthermore, 5HT increased I(Na) activation and inactivation rates mainly by increasing the transition rate from closed to open (k(C3O)) and from I(fast) to I(slow) (k(I1I2)), respectively. The antagonism of the 5HT-induced increase in I(Na) by 1-s inactivation CPs may be due an enhancement of transitions from I(fast) to I(slow), via the increase in k(I1I2). This may deplete the pool of channels residing in I(fast), reducing the frequency of reopenings from I(fast), which offsets the increase in I(Na) produced by the reduction in k(OI1). The above findings fit well with previous studies showing that activation of the cAMP/PKA cascade simultaneously increases voltage sensitive tetrodotoxin-resistant Na(+) conductance and inactivation rate in nociceptors. The antagonism of the effects of 5HT by long inactivation CPs suggests that drugs designed to induce and/or stabilize the I(slow) state might be useful for reducing hyperalgesia produced by inflammatory mediators.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-10087343, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-10388750, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-109477, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-10999938, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-11431505, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-1318516, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-1318956, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-1323671, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-1534874, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-1663796, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-1852779, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-2416892, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-2987489, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-3999040, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-447880, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-6097678, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-8538791, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-8577723, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-8592180, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-8599643, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-8887754, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-8890304, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-8899594, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-9295364, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-9714859, http://linkedlifedata.com/resource/pubmed/commentcorrection/12080097-9852572
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-3495
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5-21
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:12080097-Animals, pubmed-meshheading:12080097-Cells, Cultured, pubmed-meshheading:12080097-Cyclic AMP, pubmed-meshheading:12080097-Dose-Response Relationship, Drug, pubmed-meshheading:12080097-Electrophysiology, pubmed-meshheading:12080097-Inflammation, pubmed-meshheading:12080097-Kinetics, pubmed-meshheading:12080097-Models, Chemical, pubmed-meshheading:12080097-Nociceptors, pubmed-meshheading:12080097-Rats, pubmed-meshheading:12080097-Rats, Sprague-Dawley, pubmed-meshheading:12080097-Serotonin, pubmed-meshheading:12080097-Signal Transduction, pubmed-meshheading:12080097-Sodium, pubmed-meshheading:12080097-Sodium Channels, pubmed-meshheading:12080097-Software, pubmed-meshheading:12080097-Temperature, pubmed-meshheading:12080097-Tetrodotoxin, pubmed-meshheading:12080097-Time Factors
pubmed:year
2002
pubmed:articleTitle
Reduced transition between open and inactivated channel states underlies 5HT increased I(Na+) in rat nociceptors.
pubmed:affiliation
I.R.I.B.H.N. and Laboratory of Neurophysiology, School of Medicine, Université Libre de Bruxelles, B-1070 Brussels, Belgium.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't