Muscle contraction and inward current induced by silver and effect of Ca2+ channel blockers

Abstract

Single fibers from toe or anterior tibialis muscle contracted transiently and then tonically in the presence of 1.8 mM Ca2+ on addition of 10 microM Ag+. Exposure of fibers to Cd2+ completely inhibited tonic contraction and modified phasic contraction to some extent. Nifedipine at 10 microM initially potentiated and then completely inhibited twitch tension; subsequently, fibers no longer contracted phasically in response to 20 microM Ag+, whereas slight tonic contraction still occurred. Fibers with membrane potential clamped at -90 mV produced maintained inward current on application of Ag+. Simultaneous administration of 1 mM Cd2+ and 10 microM Ag+ to fibers voltage clamped with the double mannitol gap technique almost completely blocked the inward current. Removal of Cd2+ elicited a rapid and large inward current. Ag(+)-induced inward current was inhibited when 1 mM Cd2+ was applied to fibers during development of the inward current. In fibers paralyzed with 10 microM nifedipine, the inward current induced by 10 microM Ag+ was partially inhibited. These results suggest that phasic contraction induced by Ag+ is controlled by L-type Ca2+ channels (probably voltage sensors) located in the T-tubular membrane, whereas tonic contraction involves Ca2+ channels sensitive and/or insensitive to dihydropyridine in the surface and T-tubular membranes.

Effects of reducing agents and oxidants on excitation‐contraction coupling in skeletal muscle fibres of rat and toad.

“…At least in the cases of PCMB and Ag+, this was caused by an action on the voltage sensors (Oba et al 1992;Gonzalez et al 1993). The facts that Ag+ is effective from the extracellular side and also causes transient voltage sensor activation of Ca2P release before inactivating the coupling (Oba et al 1993), may indicate that Ag+ acts on different or additional sulfhydryl sites to those underlying the results reported here. Alternatively, the observation here that DTDP application did not cause any noticeable force response before inhibiting the coupling, might simply result from there being too few voltage sensors synchronously activated as each progresses through the activated state to the inactivated state.…”

L-Type Calcium Channel Blockers: From Diltiazem to 1,2,4-Oxadiazol-5-ones via Thiazinooxadiazol-3-one Derivatives

“…The behavior of 7a,b proves the negative inotropic effect of open chain compounds (Table 2), whereas the positive inotropic effect, observed at higher dosages, could be related, in some way, to the presence of the silver cations, known to induce contraction controlled by LTCC, thus hiding the negative inotropic activity. 23 In addition, these cations induce calcium release from the sarcoplasmic reticulum in vitro by acting on the calcium release channel and the calcium pump. 24 The Langendorff data for 7b, which is a weak LTCCs blocker at low concentrations (up to 10 -6 M, see Table 1), support the hypothesis of the positive inotropic effect due to the presence of silver cations.…”

Effects of silver ions (Ag+) on contractile ring function and microtubule dynamics during first cleavage in Ilyanassa obsoleta

“…In the more specific case of the Zlyanassa PLC contractile ring, Ag + increases the rate of PLC constriction from slow phase I constriction to fiist phase I1 constriction prematurely, during late phase I. Agt has been reported to elicit a transient phasic contraction followed by a tonic contraction in skeletal muscle [Oba et al, , 1993Oba and Hotta, 19871 by causing the release of sequestered intracellular Ca2 + from 1 he sarcoplasmic reticulum [Salama and Abramson, 1984;Gould et al, 1987;Moutin et al, 1989;Tatsumi et a1 , 1988;Brunder et al, 19881 and by increasing surface membrane per-When Ag+ is present throughout mitosis and cytokinesis, the maximally constricted PLC and the CF both encircle increased numbers of MTs compared to normal eggs (Table I) [Job et al, 1981;Keith, 1987;Sweet et al, 19881, or 2) direct binding of Caz+ to the carboxy-terminal region of tubulin in the same region where MAP2 binds to tubulin [Serrano et al, 19861. If MTs are complexed with MAPs, neither Ca2+ nor Ca2+-calmodulin disrupt them unless the MAPs have been phosphorylated [Job et al, 19851.…”

“…Silver has been shown to be a highly toxic heavy metal for fish cells [Babich et al, 19861, as well as for gastropods [Conrad, 19881, mussels [Sunila, 19881, and annelids [Koechlin and Grasset, 19881. It is an effective antibiotic against bacteria, some yeast, and some molds ISimonetti et al, 19921, has been used as an antibiotic in burn wound healing [Kuroyanagi et al, 19911 and neonatal eye care [Laga et al, 19881, and has been inccrporated in anticancer chemotherapy [Berners-Price et al, 19881. Owing at least in part to its interaction with protein thiol groups, Ag+ has been shown to increase cell membrane K+ and Na+ permeability in kidney tubules [Kone et a]., 19881 and Ca2+ permeability in skeletal muscle cells [Oba et al, 19931 and nonmuscle cells [Schnetkamp and Szerencsei, 19891, to increase lipid peroxidation in hepatocytes [Baldi et al, 19881, and to release Ca2+ from intracellular stores in muscle (Oba et al, 1993) and nonmuscle cells [Gyori et al, 19911. In the present study, in the presence of Ag+ the constriction rate of a microfilament contractile ring is increased, MT dynamics are altered to favor retention of polymerized MTs, and a transitory constriction leads to a permanent ''cell division. " Zlyanassa embryos that develop following microsurgical removal of the polar lobe at first cleavage fail to form a shell, a heart, an intestine, eyes, statocysts, or an operculum [Atkinson, 19711. Thus, during embryogenesis, toxins such as Ag+ and other heavy metals may have particularly deleterious effects.…”

“…Such a mechanism would require intracellular uptake of Ag +. Salama (Oba et al, 1993). Ag' has been shown to release Ca2+ from intracellular stores in permeabilized nonmuscle cells as well [Taguchi et al, 19911.…”