A dynamic approach reveals non‐muscle myosin influences the overall smooth muscle cross‐bridge cycling rate

Abstract

a b s t r a c tRecent evidence suggests that non-muscle myosin IIB (NMIIB) contributes to smooth muscle contraction. This study was designed to determine the effects of NMIIB on the cross-bridge cycling rate. The cross-bridge cycling rate was investigated using sinusoidal analysis. Frequency analysis revealed two asymptotes in the Bode plot of the data; and the intersection of the asymptotes (corner frequency) was higher for the B +/À strain (8.73 ± 1.10 Hz vs 16.56 ± 1.26 Hz, P < 0.05), consistent with a higher overall cross-bridge cycling rate in heterozygous NMIIB KO (B +/À ) vs WT mice. These results demonstrate that because of their long duty cycle, NMIIB cross-bridges act as an internal load on smooth muscle myosin to decrease the overall cross-bridge cycling rate and muscle V max during force maintenance.

Mechanisms of Vascular Smooth Muscle Contraction and the Basis for Pharmacologic Treatment of Smooth Muscle Disorders

“…There are three classes of nonmuscle (NM) myosin ( Golomb et al, 2004 ), NMIIA, NMIIB, and NMIIC, and both NMIIA and NMIIB are expressed in smooth muscle ( Gaylinn et al, 1989 ; Morano et al, 2000 ; Lofgren et al, 2003 ; Eddinger et al, 2007 ; Yuen et al, 2009 ; Guvenc et al, 2010 ; El-Yazbi et al, 2015 ), whereas NMIIC is only expressed in neuronal tissue ( Golomb et al, 2004 ; Jana et al, 2009 ). Both NMIIA and NMIIB are able to form bipolar thick filaments ( Billington et al, 2013 ), and similar to SM, myosin RLC phosphorylation promotes filament formation ( Ikebe and Hartshorne, 1985 ; Applegate and Pardee, 1992 ).…”

Protein kinase C activation of a blebbistatin sensitive contractile component in the wall of hypertrophying mouse urinary bladder

“…Non‐muscle myosin is expressed in smooth muscle tissues during fetal life and early after birth, and can generate contraction with slow kinetics . In some adult smooth muscle tissues, for example, the aorta, non‐muscle myosin is expressed and involved in active contractions . The role of non‐muscle myosins has been examined in different knock‐out models .…”

“…7,8 In some adult smooth muscle tissues, for example, the aorta, nonmuscle myosin is expressed and involved in active contractions. 9,10 The role of non-muscle myosins has been examined in different knock-out models. 5,6,10 Blebbistatin, a small moleculeinhibitor of actomyosin interaction, 11 has been shown to inhibit non-muscle myosin whereas smooth muscle myosin was poorly inhibited.…”

“…9,10 The role of non-muscle myosins has been examined in different knock-out models. 5,6,10 Blebbistatin, a small moleculeinhibitor of actomyosin interaction, 11 has been shown to inhibit non-muscle myosin whereas smooth muscle myosin was poorly inhibited. 12 This is consistent with a larger blebbistatin effect in the aorta and in newborn bladder tissue, 9,13 although the selectivity may not be as prominent in all tissues.…”

Vascular smooth muscle myosin light chain diphosphorylation: Mechanism, function, and pathological implications

“…Murphy's original hypothesis described this tonic force maintenance as being due to the formation of latch bridges or slowly detaching crossbridges formed on dephosphorylation of attached, phosphorylated cross-bridges. Over the years, several additional mechanisms have been proposed to explain the latch state: (i) Rembold and co-workers (86) have suggested the possibility that increased actin polymerization during sustained contraction of swine carotid arterial smooth muscle may contribute to the latch state; (ii) non-muscle myosin II expressed in smooth muscle cells has been implicated in the latch state (87)(88)(89); (iii) a comparison of the kinetic properties of smooth muscle myosin II with one or both heads phosphorylated at S19 suggested that singly phosphorylated myosin could account for latch bridge formation and the corresponding reduction in the rate of ATP consumption (90). The possibility arises that LC 20 diphosphorylation could play a role in the latch state and is certainly worth investigating.…”