Troponin I inhibitory peptide suppresses the force generation in smooth muscle by directly interfering with cross-bridge formation.
To explore possible mechanisms involving the thin filament-linked regulation of contraction in living smooth muscles, we studied the effects of a synthetic peptide of rabbit cardiac troponin I [residues 136-147] (TnIp), which is a minimal sequence required to inhibit striated muscle acto-tropomyosin-myosin ATPase activity, on the mechanical properties of beta-escin skinned preparations of taenia caeci from guinea pig. TnIp reversibly suppressed the Ca(2+)-activated force without significant effects on the Ca(2+) sensitivity and on the phosphorylation level of myosin regulatory light chain (MLC(20)). TnIp also reversibly suppressed the Ca(2+)/calmodulin-independent contraction induced by 30mM Mg(2+). An analogue of TnIp, which lost inhibiting action on acto-tropomyosin-myosin ATPase activity, affected neither Ca(2+)-activated nor 30mM Mg(2+)-induced contraction. These results indicate that TnIp suppresses the force generation in smooth muscle by directly interfering with cross-bridge formation rather than inhibiting the Ca(2+)/calmodulin-dependent thick and thin filament activating processes.
Watanabe
Masaru
M
Department of Physiology, Tokyo Medical University, Tokyo, Japan. masaru@tokyo-med.ac.jp
Yoshino
Yasumasa
Y
Morimoto
Sachio
S
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D006168:Guinea Pigs; D008274:Magnesium / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011817:Rabbits; D019210:Troponin I / Q000235:genetics / Q000378:metabolism*
D002147:Calmodulin; D018994:Myosin Light Chains; D010446:Peptide Fragments; D019210:Troponin I; D009218:Myosins; D008274:Magnesium; D002118:Calcium