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  • Title: Effects of tetracaine and procaine on skinned muscle fibres depend on free calcium.
    Author: Pike GK, Abramson JJ, Salama G.
    Journal: J Muscle Res Cell Motil; 1989 Oct; 10(5):337-49. PubMed ID: 2556441.
    Abstract:
    The local anaesthetics, tetracaine and procaine have previously been found to block, induce or potentiate Ca2+ release from the sarcoplasmic reticulum (SR) of skeletal muscle depending on the preparation, experimental conditions and design. We now show that low concentrations of tetracaine and procaine block SR Ca2+ release whereas high concentrations induce release from the SR of amphibian and mammalian skinned fibres. Both actions depend on pCa, such that a shift in pCa can alter their effect from blocking to releasing Ca2+. In skinned fibres with Ca2+-loaded SR, tetracaine (1 mM) produced a tonic contraction with a time to half-peak of 15-20 s and a magnitude reaching 80% of maximum force. Ca2+ release by tetracaine or procaine occurred at pCa less than or equal to 6.5 and was not blocked by Ruthenium Red (RR) (25 mM). This action of tetracaine was attributed to SR Ca2+ release rather than to a displacement of bound Ca2+ because fibres lacking a functional SR due to pre-treatment with quercetin (100 mM), A 23187 (100 micrograms ml-1) or Triton X-100 (1%) did not contract after additions of tetracaine. Lower concentrations of tetracaine (0.5 mM) and procaine (less than or equal to 10 mM) blocked contractions due to caffeine (at pCa greater than or equal to 6.73), sulphydryl oxidizing agents, or Ca2+-induced Ca2+ release (CICR). The inhibition of CICR as a function of pCa was difficult to measure quantitatively since lowering pCa to elicit CICR twitches was sufficient to initiate tetracaine-induced tonic contractions. Experiments with isolated SR vesicles showed that 1 mM tetracaine inhibited CICR, over a wide range of pCa but 3-5 mM tetracaine induced rapid Ca2+ release. The opposite effects of tetracaine and procaine depend mostly on their concentration in SR vesicles and/or pCa in skinned fibres. Blockade of release seems to occur via the CICR pathway, and induction of release through an increase in SR membrane permeability.
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