Abstract
Mice deficient in the smooth muscle Cav1.2 calcium channel (SMACKO, smooth muscle alpha1c-subunit calcium channel knockout) have a severely reduced micturition and an increased bladder mass. L-type calcium current, protein, and spontaneous contractile activity were absent in the bladder of SMACKO mice. K+ and carbachol (CCh)-induced contractions were reduced to 10-fold in detrusor muscles from SMACKO mice. The dihydropyridine isradipine inhibited K+- and CCh-induced contractions of muscles from CTR but had no effect in muscles from SMACKO mice. CCh-induced contraction was blocked by removing extracellular Ca2+ but was unaffected by the PLC inhibitor U73122 or depletion of intracellular Ca2+ stores by thapsigargin. In muscles from CTR and SMACKO mice, CCh-induced contraction was partially inhibited by the Rho-kinase inhibitor Y27632. These results show that the Cav1.2 Ca2+ channel is essential for normal bladder function. The Rho-kinase and Ca2+-release pathways cannot compensate the lack of the L-type Ca2+ channel.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amides / pharmacology
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Animals
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Calcium / metabolism
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Calcium Channels, L-Type / deficiency
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Calcium Channels, L-Type / genetics
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Calcium Channels, L-Type / physiology*
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Carbachol / pharmacology
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Enzyme Inhibitors / pharmacology
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Estrenes / pharmacology
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Intracellular Signaling Peptides and Proteins
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Ion Channel Gating
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Ion Transport / drug effects
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Isradipine / pharmacology
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Mice
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Mice, Knockout
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects*
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Muscle, Smooth / physiopathology
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Patch-Clamp Techniques
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / physiology
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Pyridines / pharmacology
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Pyrrolidinones / pharmacology
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Receptors, Muscarinic / drug effects
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Receptors, Muscarinic / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Thapsigargin / pharmacology
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Urinary Bladder / physiology*
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Urination Disorders / genetics
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Urination Disorders / physiopathology
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rho-Associated Kinases
Substances
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Amides
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Calcium Channels, L-Type
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Enzyme Inhibitors
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Estrenes
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Intracellular Signaling Peptides and Proteins
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L-type calcium channel alpha(1C)
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Pyridines
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Pyrrolidinones
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Receptors, Muscarinic
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Y 27632
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Thapsigargin
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Carbachol
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Protein Serine-Threonine Kinases
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rho-Associated Kinases
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Calcium
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Isradipine