Effects of tetracaine and procaine on skinned muscle fibres depend on free calcium |
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Authors: | Gregory K Pike Jonathan J Abramson Guy Salama |
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Institution: | (1) Department of Physiology, University of Pittsburgh School of Medicine, 15261 Pittsburgh, Pennsylvania, USA;(2) Department of Physics, Environmental Sciences and Resources Program, Portland State University, 97207 Portland, Oregon, USA |
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Abstract: | Summary 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 (1mm) 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 occured at pCa 6.5 and was not blocked by Ruthenium Red (RR) (25 m). 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 m), A 23187 (100 g ml–1) or Triton X-100 (1%) did not contract after additions of tetracaine. Lower concentrations of tetracaine (0.5mm) and procaine ( 10mm) blocked contractions due to caffeine (at pCa 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 1mm tetracaine inhibited CICR, over a wide range of pCa but 3–5mm 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.Abbreviations SR
sarcoplasmic reticulum
- HEPES
N-2-hydroxy-ethylpiperazine-N1-2-ethanesulphonic acid
- EGTA
ethylene glycol bis ( -aminoethyl ether)-N,N,N1,-N1-tetraacetic acid
- CICR
Ca2+-induced Ca2+ release
- MOPS
morpholinopropane sulphonic acid
- RR
Ruthenium Red |
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