Inhibition of TnI-TnC interaction and contraction of skinned muscle fibres by the synthetic peptide TnI [104-115].
Circular dichroism was used to study the induction of helix in TnC or TnI-TnC by the TnI peptide [104-115] at various Ca2+ concentrations. The increase in negative ellipticity and pCa2+ values for the peptide-TnC complex, indicates that binding of the peptide to TnC, induces a small helical conformational change in TnC. This results in an increase in the Ca2+ binding constant and the pCa50 value required to induce 50% of Ca2+ -dependent helix in TnC. The introduction of the peptide to a preformed mixture of TnI-TnC resulted in an increase in negative ellipticity and a decrease in the pCa50 and the apparent Ca2+ binding constant towards the values obtained for the TnI peptide-TnC complex and away from those of TnI-TnC. This demonstrates that the TnI peptide can successfully compete with TnI for TnC and thereby inhibit the TnI-TnC interaction. The addition of the TnI peptide to skinned rabbit psoas or porcine cardiac fibres resulted in the inhibition of the force development and a decrease in the pCa50 values required for 50% Ca2+ activation. The magnitude of the inhibition of tension development and the shift in the Ca2+ sensitivity for skinned cardiac muscle fibres was approximately half that observed with skeletal muscle fibres. In view of the CD findings, these skinned fibre results can be accounted for by the peptide inhibiting the TnI interaction with TnC. However, it is possible that the TnI peptide also has a direct inhibitory effect on TM-actin.(ABSTRACT TRUNCATED AT 250 WORDS)
Rüegg
J C
JC
II. Physiologisches Institut, Universität Heidelberg, Federal Republic of Germany.
Zeugner
C
C
Van Eyk
J
J
Kay
C M
CM
Hodges
R S
RS
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002942:Circular Dichroism; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D011487:Protein Conformation / Q000187:drug effects; D011817:Rabbits; D013552:Swine; D014336:Troponin / Q000378:metabolism* / Q000494:pharmacology*; D019209:Troponin C; D019210:Troponin I; D014862:Wasp Venoms / Q000494:pharmacology
D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; D014336:Troponin; D019209:Troponin C; D019210:Troponin I; D014862:Wasp Venoms; C037500:mastoparan; C061291:troponin I (104-115); D002118:Calcium