Document Detail


KCNQ/M-currents contribute to the resting membrane potential in rat visceral sensory neurons.
MedLine Citation:
PMID:  16777937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The M-current is a slowly activating, non-inactivating potassium current that has been shown to be present in numerous cell types. In this study, KCNQ2, Q3 and Q5, the molecular correlates of M-current in neurons, were identified in the visceral sensory neurons of the nodose ganglia from rats through immunocytochemical studies. All neurons showed expression of each of the three proteins. In voltage clamp studies, the cognition-enhancing drug linopirdine (1-50 microM) and its analogue, XE991 (10 microM), quickly and irreversibly blocked a small, slowly activating current that had kinetic properties similar to KCNQ/M-currents. This current activated between -60 and -55 mV, had a voltage-dependent activation time constant of 208 +/- 12 ms at -20 mV, a deactivation time constant of 165 +/- 24 ms at -50 mV and V1/2 of -24 +/- 2 mV, values which are consistent with previous reports for endogenous M-currents. In current clamp studies, these drugs also led to a depolarization of the resting membrane potential at values as negative as -60 mV. Flupirtine (10-20 microM), an M-current activator, caused a 3-14 mV leftward shift in the current-voltage relationship and also led to a hyperpolarization of resting membrane potential. These data indicate that the M-current is present in nodose neurons, is activated at resting membrane potential and that it is physiologically important in regulating excitability by maintaining cells at negative voltages.
Authors:
Cynthia L Wladyka; Diana L Kunze
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-06-15
Journal Detail:
Title:  The Journal of physiology     Volume:  575     ISSN:  0022-3751     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-16     Completed Date:  2006-10-06     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  175-89     Citation Subset:  IM    
Affiliation:
Rammelkamp Centre for Research and Education R326 MetroHealth Medical Centre, 2500 MetroHealth Drive, Cleveland, OH 44109-1998, USA.
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MeSH Terms
Descriptor/Qualifier:
Aminopyridines / pharmacology
Animals
Anthracenes / pharmacology
Cells, Cultured
Dose-Response Relationship, Drug
Indoles / pharmacology
KCNQ Potassium Channels / analysis,  drug effects,  metabolism*
KCNQ2 Potassium Channel / analysis,  drug effects,  metabolism*
KCNQ3 Potassium Channel / analysis,  drug effects,  metabolism*
Membrane Potentials
Neurons, Afferent / chemistry,  drug effects,  metabolism*
Nodose Ganglion / chemistry,  drug effects,  physiology*
Potassium / metabolism
Potassium Channel Blockers / pharmacology
Pyridines / pharmacology
Rats
Rats, Sprague-Dawley
Visceral Afferents / chemistry,  drug effects,  metabolism*
Grant Support
ID/Acronym/Agency:
HL25830/HL/NHLBI NIH HHS; HL61436/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; 0/Aminopyridines; 0/Anthracenes; 0/Indoles; 0/KCNQ Potassium Channels; 0/KCNQ2 Potassium Channel; 0/KCNQ3 Potassium Channel; 0/Kcnq2 protein, rat; 0/Kcnq3 protein, rat; 0/Kcnq5 protein, rat; 0/Potassium Channel Blockers; 0/Pyridines; 105431-72-9/linopirdine; 56995-20-1/flupirtine; 7440-09-7/Potassium
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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