Linked Life Data

21300746

Source:http://linkedlifedata.com/resource/pubmed/id/21300746

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 7
pubmed:dateCreated
2011-4-13
pubmed:abstractText
The large conductance calcium- and voltage-activated potassium channel (BK channel) and its smooth muscle-specific ?1 subunit regulate excitation–contraction coupling in many types of smooth muscle cells. However, the relative contribution of BK channels to control of M2- or M3-muscarinic acetylcholine receptor mediated airway smooth muscle contraction is poorly understood. Previously, we showed that knockout of the BK channel ?1 subunit enhances cholinergic-evoked trachea contractions. Here, we demonstrate that the enhanced contraction of the BK ?1 knockout can be ascribed to a defect in BK channel opposition of M2 receptor-mediated contractions. Indeed, the enhanced contraction of ?1 knockout is eliminated by specific M2 receptor antagonism. The role of BK ?1 to oppose M2 signalling is evidenced by a greater than fourfold increase in the contribution of L-type voltage-dependent calcium channels to contraction that otherwise does not occur with M2 antagonist or with ?1 containing BK channels. The mechanism through which BK channels oppose M2-mediated recruitment of calcium channels is through a negative shift in resting voltage that offsets, rather than directly opposes, M2-mediated depolarization. The negative shift in resting voltage is reduced to similar extents by BK ?1 knockout or by paxilline block of BK channels. Normalization of ?1 knockout baseline voltage with low external potassium eliminated the enhanced M2-receptor mediated contraction. In summary, these findings indicate that an important function of BK/?1 channels is to oppose cholinergic M2 receptor-mediated depolarization and activation of calcium channels by restricting excitation–contraction coupling to more negative voltage ranges.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1469-7793
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
589
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1803-17
pubmed:meshHeading
pubmed-meshheading:21300746-Animals, pubmed-meshheading:21300746-Calcium Channels, L-Type, pubmed-meshheading:21300746-Excitation Contraction Coupling, pubmed-meshheading:21300746-Indoles, pubmed-meshheading:21300746-Large-Conductance Calcium-Activated Potassium Channel..., pubmed-meshheading:21300746-Membrane Potentials, pubmed-meshheading:21300746-Mice, pubmed-meshheading:21300746-Mice, Inbred C57BL, pubmed-meshheading:21300746-Mice, Knockout, pubmed-meshheading:21300746-Models, Biological, pubmed-meshheading:21300746-Muscarinic Antagonists, pubmed-meshheading:21300746-Muscle, Smooth, pubmed-meshheading:21300746-Muscle Contraction, pubmed-meshheading:21300746-Pirenzepine, pubmed-meshheading:21300746-Potassium Channel Blockers, pubmed-meshheading:21300746-Receptor, Muscarinic M2, pubmed-meshheading:21300746-Respiratory Mechanics, pubmed-meshheading:21300746-Signal Transduction, pubmed-meshheading:21300746-Trachea
pubmed:year
2011
pubmed:articleTitle
BK channel ?1 subunits regulate airway contraction secondary to M2 muscarinic acetylcholine receptor mediated depolarization.
pubmed:affiliation
Department of Physiology, UT Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural