An essential role of Cav1.2 L-type calcium channel for urinary bladder function

FASEB J. 2004 Jul;18(10):1159-61. doi: 10.1096/fj.04-1516fje. Epub 2004 May 7.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / deficiency
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / physiology*
  • Carbachol / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Estrenes / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Ion Channel Gating
  • Ion Transport / drug effects
  • Isradipine / pharmacology
  • Mice
  • Mice, Knockout
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiopathology
  • Patch-Clamp Techniques
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / physiology
  • Pyridines / pharmacology
  • Pyrrolidinones / pharmacology
  • Receptors, Muscarinic / drug effects
  • Receptors, Muscarinic / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thapsigargin / pharmacology
  • Urinary Bladder / physiology*
  • Urination Disorders / genetics
  • Urination Disorders / physiopathology
  • rho-Associated Kinases

Substances

  • Amides
  • Calcium Channels, L-Type
  • Enzyme Inhibitors
  • Estrenes
  • Intracellular Signaling Peptides and Proteins
  • L-type calcium channel alpha(1C)
  • Pyridines
  • Pyrrolidinones
  • Receptors, Muscarinic
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Y 27632
  • Thapsigargin
  • Carbachol
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases
  • Calcium
  • Isradipine