ATP ANALOGS AND MUSCLE-CONTRACTION - MECHANICS AND KINETICS OF NUCLEOSIDE TRIPHOSPHATE-BINDING AND HYDROLYSIS

The mechanical behavior of skinned rabbit psoas muscle fiber contracti ons and in vitro motility of F-actin (V-f) have been examined using AT P, CTP, UTP, or their 2-deoxy forms (collectively designated as nucleo tide triphosphates or NTPs) as contractile substrates. Measurements of actin-activated heavy meromyosin (HMM) NTPase, the rates of NTP bindi ng to myosin and actomyosin, NTP-mediated acto-HMM dissociation, and N TP hydrolysis by acto-HMM were made for comparison to the mechanical r esults. The data suggest a very similar mechanism of acto-HMM NTP hydr olysis. Whereas all NTPs studied support force production and stiffnes s that vary by a factor 2 or less, the unloaded shortening velocity (V -u) of muscle fibers varies by almost 10-fold. 2-Deoxy ATP (dATP) was unique in that V-u was 30% greater than with ATP. Parallel behavior wa s observed between V-f and the steady-state maximum actin-activated HM M ATPase rate. Further comparisons suggest that the variation in force correlates with the rate and equilibrium constant for NTP cleavage; t he variations in V-u or V-f are related to the rate of cross-bridge di ssociation caused by NTP binding or to the rate(s) of product release.