Distinct contractile systems for electromechanical and pharmacomechanical coupling in smooth muscle.
Electromechanical coupling by KCl depolarization of bladder preparations elicits an initial phasic and subsequent tonic contraction. Using a smooth-muscle myosin heavy chain (SM-MyHC) knock-out mouse model we could previously demonstrate, that phasic and tonic contraction of intact neonatal bladder preparations could be elicited through the recruitment of SM-MyHC and non-muscle myosin heavy chains (NM-MyHC), respectively. Inhibition of myosin light chain kinase (MLCK) by ML-7 eliminated the phasic contraction of wild-type (+/+), rather than tonic contraction of neonatal bladder strips prepared from both +/+ and homozygous SM-MyHC knock-out (-/-) mice. Pharmacomechanical coupling upon PDBu-induced activation of protein kinase C of neonatal bladder preparations elicited tonic contraction of both +/+ and -/- murine. We suggest that: i) electromechanical coupling activates both SM-MyHC and NM-MyHC systems via a ML-7 sensitive and insensitive pathway, respectively. ii) Pharmacomechanical coupling recruits part of the NM-MyHC system rather than SM-MyHC.
Lamounier-Zepter
Valéria
V
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Baltas
Leonidas G
LG
Morano
Ingo
I
D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D001381:Azepines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005091:Exons; D005838:Genotype; D006720:Homozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000166:cytology*; D009218:Myosins / Q000737:chemistry*; D009281:Naphthalenes / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism
D001381:Azepines; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D020033:Protein Isoforms; C070571:ML 7; D015240:Phorbol 12,13-Dibutyrate; D011189:Potassium Chloride; D011493:Protein Kinase C; D009218:Myosins