ATP analogs and muscle contraction: mechanics and kinetics of nucleoside triphosphate binding and hydrolysis.
The mechanical behavior of skinned rabbit psoas muscle fiber contractions and in vitro motility of F-actin (Vf) have been examined using ATP, CTP, UTP, or their 2-deoxy forms (collectively designated as nucleotide triphosphates or NTPs) as contractile substrates. Measurements of actin-activated heavy meromyosin (HMM) NTPase, the rates of NTP binding to myosin and actomyosin, NTP-mediated acto-HMM dissociation, and NTP hydrolysis by acto-HMM were made for comparison to the mechanical results. The data suggest a very similar mechanism of acto-HMM NTP hydrolysis. Whereas all NTPs studied support force production and stiffness that vary by a factor 2 or less, the unloaded shortening velocity (Vu) of muscle fibers varies by almost 10-fold. 2-Deoxy ATP (dATP) was unique in that Vu was 30% greater than with ATP. Parallel behavior was observed between Vf and the steady-state maximum actin-activated HMM ATPase rate. Further comparisons suggest that the variation in force correlates with the rate and equilibrium constant for NTP cleavage; the variations in Vu or Vf are related to the rate of cross-bridge dissociation caused by NTP binding or to the rate(s) of product release.
Regnier
M
M
Department of Physiology, School of Medicine, University of California, Los Angeles 90095, USA.
Lee
D M
DM
Homsher
E
E
D017766:Acid Anhydride Hydrolases / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D005260:Female; D006868:Hydrolysis; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D015879:Myosin Subfragments / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D043583:Nucleoside-Triphosphatase; D011817:Rabbits; D012265:Ribonucleotides / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
D015879:Myosin Subfragments; D012265:Ribonucleotides; D000255:Adenosine Triphosphate; D000205:Actomyosin; D017766:Acid Anhydride Hydrolases; D043583:Nucleoside-Triphosphatase; D009218:Myosins