Molecular basis of the catch state in molluscan smooth muscles: a catchy challenge

Abstract

The catch state (or 'catch') of molluscan smooth muscles is a passive holding state that occurs after cessation of stimulation. During catch, force and, in particular, resistance to stretch are maintained for long time periods with low (or no) energy consumption at basal intracellular free [Ca2+]. The catch state is initiated by Ca2+-stimulated dephosphorylation of the titin-like protein twitchin and is inhibited by cAMP-dependent phosphorylation of twitchin. In addition, catch is pH sensitive, but the reason for this is unknown. According to a traditional model, catch is due to slower cross-bridge cycles where myosin heads remain longer attached to the actin filaments after force generation, possibly caused by a hindered release of ADP from the myosin heads. However, this model was disproved by recent findings which showed that (i) inhibitors of myosin function, such as vanadate, do not affect catch force; (ii) factors which terminate the catch state do not accelerate myosin head detachment kinetics and (iii) a catch-like high resistance to stretch is still inducible when force development is prevented. Thus, catch probably involves passive linkage structures interconnecting the myofilaments (catch linkages). For example twitchin could (i) tie myosin heads to the thin filaments, (ii) mechanically lock them in a stretch resistant state or (iii) interconnect thick and thin filaments directly. However, it is questionable if these mechanisms are sufficient since twitchin seems to be about 15-times less abundant than myosin. Therefore, in addition, interconnections between thick filaments could exist, which could involve e.g. paramyosin or twitchin. Catch could even involve changes in the compliance of thick filaments. The function of myorod, found specifically in catch muscles in equal abundance with myosin, is not known. The suggestion is made here that catch linkages are present already during active contraction either as ratchet-like elements resisting stretch and not opposing shortening or in some kind of 'standby' mode ready to transform suddenly into the working mode by stretches or after Ca2+ removal following cessation of stimulation.

The highly efficient holding function of the mollusc ‘catch’ muscle is not based on decelerated myosin head cross-bridge cycles

“…When Ca 2þ returns to basal levels after the end of stimulation, catch linkages apparently remain stable as long as no cAMP-dependent phosphorylation occurs. Based on published data, catch appeared to occur only after an active contraction (see review by Galler 2008). However, this study has shown that a direct transition from the relaxed state to the catch state is possible without force activation, as long as the level of Ca 2þ rises during stimulation to activate the calcineurin-like phosphatase responsible for the dephosphorylation of twitchin.…”

“…This study also offers an answer to a long-standing question, highlighted in the review by Galler (2008): whether the linkage structures carrying catch force (catch linkages) are formed during the stimulation phase or only after the end of stimulation. As shown in figures 2c and 3b, a serotonin/cAMP-sensitive stiffness already appears during the stimulation phase (at least in a standby mode; Galler 2008) (acetylcholine/Ca 2þ in intact/permeabilized preparations, respectively) and remains high after the end of stimulation in the subsequent catch phase.…”

“…As twitchin seems to be 15 times less abundant than myosin (Funabara et al 2005), the number of twitchin-based catch linkages can only be small. Interconnections between longitudinally displaced thick filaments could further contribute to form a rigid myofilament network during catch (for reviews, see Rü egg 1971;Galler 2008). This hypothesis is supported by electron microscopic studies showing interconnections among thick filaments during catch (Heumann & Zebe 1968;Gilloteaux & Baguet 1977;Takahashi et al 2003).…”

“…This finding directly validates the current view about the regulation of catch described in §1. Hitherto, this view was to a certain degree speculative, as it was based only on a number of (indirect) observations and conclusions (for a review, see Galler 2008). Thus, catch linkages (at least in a standby mode) are the immediate product of a dephosphorylation reaction executed by a calcineurin-like phosphatase that is activated by the Ca 2þ increase during muscle stimulation.…”

“…The identity of structures responsible for the state of catch is a matter for speculation (Galler 2008). Catch could be due to passive linkages interconnecting thick filaments with actin filaments.…”