Linked Life Data

17651721

Source:http://linkedlifedata.com/resource/pubmed/id/17651721

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2007-10-1
pubmed:abstractText
Calcium currents (I(Ca)) in inner hair cells (IHCs) are carried by the Ca(v)1.3 subtype of L-type calcium channels. They play an important role in synaptic transmission of sound-evoked mechanical stimuli. L-type calcium channels are targets of the organic blocker classes dihydropyridines, phenylalkylamines and benzothiazepines. Previously a low sensitivity of the Ca(v)1.3 subtype towards dihydropyridines has been demonstrated. Therefore, this study evaluates the effect of two phenylalkylamines (verapamil and gallopamil) and the benzothiazepine diltiazem on I(Ca) through Ca(v)1.3 channels in mouse IHCs. Whole-cell I(Ca) was measured using the patch-clamp technique in mouse IHCs aged postnatal day 3-7 with 5 mM calcium as a charge carrier. The phenylalkylamines verapamil and gallopamil and the benzothiazepine diltiazem inhibited I(Ca) in IHCs in a concentration-dependent manner. This block was largely reversible. Dose-response curves revealed IC(50) values of 199+/-19 microM for verapamil, 466+/-151 microM for gallopamil and 326+/-67 microM for diltiazem. The inhibition of peak I(Ca) by phenylalkylamines and benzothiazepines was voltage-independent. Verapamil (300 microM) enhanced current inactivation from -20 to +20 mV while diltiazem (300 microM) did so only at very depolarised potentials (+20 mV). In conclusion, the concentrations of phenylalkylamines and benzothiazepine necessary to inhibit 50% of I(Ca) in IHCs were one order larger compared to concentrations which inhibited I(Ca) through Ca(v)1.2 channels in native cells or expression systems. However, inhibitory concentrations were in the same range as those required for block of I(Ca) in turtle hair cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
573
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39-48
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Effects of phenylalkylamines and benzothiazepines on Ca(v)1.3-mediated Ca2+ currents in neonatal mouse inner hair cells.
pubmed:affiliation
Slovak Academy of Sciences, Institute of Molecular Physiology and Genetics, Vlárska 5, 833 34 Bratislava, Slovak Republic. bohumila.tarabova@savba.sk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't