Activation of the contractile apparatus of skinned fibres of frog by the divalent cations barium, cadmium and nickel.

Abstract

SUMMARY1. The contractile apparatus of mechanically skinned muscle fibres of frog can be reversibly activated by Ba2+ and Cd2 .2. The maximum force induced by both Ba2+ and Cd2+ is the same as that induced by Ca2+ and Sr2+.3. The ionic concentrations of the divalent cations required to induce 50 % of the maximum activated force at 1 mM-Mg2+, pH 7410, 22 TC and 250 mm ionic strength are about 8 x 10-7 M for Ca2+, 5 X 10-6 M for Cd2+, 2-6 x 10-5 M for Sr2+ and 7 x 10-4 M for Ba2+.4. Exposure of the skinned fibre to relatively low Ni2+ concentrations (between 10-6 and 10-5 M) resulted in a transient force response accompanied by an irreversible change in the ability of the preparation to develop force.5. The Ba2+-and Cd2+-activation curves are considerably flatter than the corresponding curves for Ca2+ and Sr2+.6. An increase in Mg2+ concentration from 1 to 3 mm decreased the sensitivity of the contractile apparatus to Ba2+ by a factor of about 1P5 without affecting the maximum force response.7. The Ca2+-activation curve was modified in the presence of subthreshold concentrations of Ba2+ and the results indicate that Ba2+ could have both an activating and an inhibitory action on the Ca2+-activated force.8. A kinetic model which can quantitatively explain the results for activation of contraction by Ba2+ and Ca2+, is described.

Activation of troponin C by Cd2+ and Pb2+

“…Conceivably, the regulatory sites are the attack sites of the heavy metals. Indeed, Cd 2+ can induce skinned muscle contraction, and the maximum force generated is the same as that of Ca2+; its concentration giving half maximum force is 5 x 10 -6 M (Stephenson et al 1986). Rats receiving Cd 2+ or Pb 2+ in drinking water (1 ppm) exhibited a progressive increase in systolic pressure (Kopp et al 1985).…”

Adjacent asparagines in the NR2‐subunit of the NMDA receptor channel control the voltage‐dependent block by extracellular Mg2+

“…For the extracellular solutions, the 10 mÒ BAPTA was replaced by 8 mÒ EGTA and 2 mÒ EDTA (0 Mg¥ control solution) or 10 mÒ EGTA to which MgClµ was added to yield the free Mg¥ concentration indicated in the text. Free Mg¥ concentrations were determined from apparent affinity constants for EGTA, measured with the potentiometric method, with software kindly provided by R. Thieleczek (Moisescu & Thieleczek, 1978;Stephenson & Thieleczek, 1986). In all instances block was measured using whole-cell recordings of HEK 293 cells.…”

Sulphydryl reagents trigger Ca2+ release from the sarcoplasmic reticulum of skinned rabbit psoas fibres.

“…However, the omission of ATP-regenerating systems is of little consequence to force measurements when fibre diameters are in the range of 100 tm and the diffusion of ATP to the centre of the fibres is rapid compared to rates of ATP hydrolysis, as is the case for fibres bathed in millimolar ATP (Ferenczi, Goldman & Simmons, 1984) and high ionic-strength solutions to reduce ATPase activity (Yanagida, Kuranaga & Inoue, 1982). Previous studies on the interaction of Cd2+, Ag+ or Hg2+ with skinned fibres also omitted ATP-regenerating systems (Stephenson & Thieleczek, 1986, Oba et al 1989 an ATP-regenerating system (15 mM-CP plus 50 U ml-1 CK did not change either the time course or the amplitude of forces generated during Cal+-induced Ca 2 release (n = 6) or caffeine (n = 4) contractions, or contractures induced by a pCa of 2 (n = 6) (not shown). Possible fibre rundown.…”