Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 2
pubmed:dateCreated
2004-12-6
pubmed:abstractText
We investigated, by using the patch clamp technique, Ca2+-mediated regulation of heterologously expressed TRPC6 and TRPC7 proteins in HEK293 cells, two closely related homologues of the transient receptor potential (TRP) family and molecular candidates for native receptor-operated Ca2+ entry channels. With nystatin-perforated recording, the magnitude and time courses of activation and inactivation of carbachol (CCh; 100 microM)-activated TRPC6 currents (I(TRPC6)) were enhanced and accelerated, respectively, by extracellular Ca2+ (Ca2+(o)) whether it was continuously present or applied after receptor stimulation. In contrast, Ca2+(o) solely inhibited TRPC7 currents (I(TRPC7)). Vigorous buffering of intracellular Ca2+ (Ca2+(i)) under conventional whole-cell clamp abolished the slow potentiating (i.e. accelerated activation) and inactivating effects of Ca2+(o), disclosing fast potentiation (EC50: approximately 0.4 mM) and inhibition (IC50: approximately 4 mM) of I(TRPC6) and fast inhibition (IC50: approximately 0.4 mM) of I(TRPC7). This inhibition of I(TRPC6) and I(TRPC7) seems to be associated with voltage-dependent reductions of unitary conductance and open probability at the single channel level, whereas the potentiation of I(TRPC6) showed little voltage dependence and was mimicked by Sr2+ but not Ba2+. The activation process of I(TRPC6) or its acceleration by Ca2+(o) probably involves phosphorylation by calmodulin (CaM)-dependent kinase II (CaMKII), as pretreatment with calmidazolium (3 microM), coexpression of Ca2+-insensitive mutant CaM, and intracellular perfusion of the non-hydrolysable ATP analogue AMP-PNP and a CaMKII-specific inhibitory peptide all effectively prevented channel activation. However, this was not observed for TRPC7. Instead, single CCh-activated TRPC7 channel activity was concentration-dependently suppressed by nanomolar Ca2+(i) via CaM and conversely enhanced by IP3. In addition, the inactivation time course of I(TRPC6) was significantly retarded by pharmacological inhibition of protein kinase C (PKC). These results collectively suggest that TRPC6 and 7 channels are multiply regulated by Ca2+ from both sides of the membrane through differential Ca2+-CaM-dependent and -independent mechanisms.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-10230783, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-10381584, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-10488066, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-10545143, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-10611319, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-10790163, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-10793239, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11015619, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11029277, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11096123, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11179201, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11248050, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11290752, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11389472, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11788346, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11826271, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11861411, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11917094, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-11983166, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12030534, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12032305, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12196518, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12377790, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12379180, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12456670, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12686753, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12765690, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12857742, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-12972630, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-15023993, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-15268627, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-15489249, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-1621949, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-1667799, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-1724672, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-2118179, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-7478930, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-7529832, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-7778873, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-8568664, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9211799, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9298988, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9345310, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9512398, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9553080, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9560440, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9674696, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9769417, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9853757, http://linkedlifedata.com/resource/pubmed/commentcorrection/15579537-9930701
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3751
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
561
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
415-32
More...