PubMed · 11240890
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I Murat. 2001. Halothane: the last word?. https://doi.org/10.1046/j.1460-9592.2001.0666c.x
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The effect of cytosolic Mg2+ on halothane-induced Ca2+ release from the sarcoplasmic reticulum (SR) was investigated in mechanically skinned fibres from the rat extensor digitorum longus (EDL) muscle. Preparations were perfused with solutions mimicking the intracellular milieu and changes in [Ca2+] were detected using Fura-2 fluorescence. In the presence of 1 mM Mg2+, brief (500 ms) applications of 40 mM halothane failed to induce Ca2+ release from the SR. However, Ca2+ release became detectable when [Mg2+] was reduced to 0.4 mM, and the amplitude of the response increased progressively as [Mg2+] was further reduced to 0.2 and 0.1 mM. Lower halothane concentrations within the range found during anaesthesia or induction (0.1-1.2 mM) failed to induce SR Ca2+ release at 0.2 or 0.4 mM Mg2+. However, in further experiments, preparations were exposed to 1 mM halothane for 2-3 min under conditions where the volume of solution surrounding the preparation was restricted by stopping the flow. In the absence of perfusion, 1 mM halothane induced Ca2+ release from the SR at 0.4 mM Mg2+ in two out of six preparations, and release was observed consistently at 0.2 and 0.1 mM Mg2+. Responses to 1 mM halothane induced in the presence of 0.4 and 0.2 mM Mg2+ were typically delayed in onset and involved a localised release of Ca2+ that propagated along the fibre. These results suggest that halothane-induced Ca2+ release is strongly inhibited at normal physiological levels of Mg2+. However, when Mg2+-induced inhibition of the ryanodine receptor (RYR) is reduced, levels of halothane within the range found during anaesthesia can induce a marked efflux of Ca2+ from the SR. This may be of relevance to the condition of malignant hyperthermia, where the inhibition of RYRs by Mg2+ is reportedly reduced.
The thalamocortical network is characterized by rhythmic burst activity during natural sleep and tonic single-spike activity during wakefulness. The change between these two activity modes is partially governed by transmitters acting on leak K+ currents in the thalamus, although the nature of the constituting ion channels is not yet known. In the present study, the contribution of members of the two-pore domain K+ channel family to the leak current was investigated using whole-cell patch-clamp techniques and molecular biological techniques. RT-PCR and in situ hybridization revealed the expression of TWIK-related acid-sensitive K+ channel 1 (TASK 1) and TASK3 channels in the rat dLGN. Voltage-clamp recordings of thalamocortical relay neurons in slice preparations demonstrated the existence of a current component sensitive to the TASK channel blocker bupivacaine, which reversed at the presumed K+ equilibrium potential, showed outward rectification, and contributed approximately 40% to the standing outward current at depolarized values of the membrane potential (-28 mV). The pharmacological profile was indicative of TASK channels, in that the current was sensitive to changes in extracellular pH, reduced by muscarine and increased by halothane, and these effects were occluded by a near-maximal action of bupivacaine. Pharmacological manipulation of this current under current-clamp conditions resulted in a shift between burst and tonic firing modes. It is concluded that TASK1 and TASK3 channels contribute to the muscarine- and halothane-sensitive conductance in thalamocortical relay neurons, thereby contributing to the change in the activity mode of thalamocortical networks observed during the sleep-wake cycle and on application of inhalational anesthetics.
We demonstrate here unexpectedly long-lasting effect of transcutaneous electrical nerve stimulation (TENS) to alleviate thermal hyperalgesia in rats with peripheral neuropathy produced by constriction of sciatic nerve. For TENS groups, electrical stimulation for 16.7 min (1 Hz, paired current, 12 mA, 5-ms interval, 0.2-ms duration, 999 pairs), once a day, was delivered for 5 consecutive days, under halothane anesthesia (Hal-TENS group) or pentobarbital anesthesia (Pent-TENS group). For non-TENS groups, only the anesthesia was delivered (Hal-no TENS group, Pent-no TENS group). For the control group, neither anesthetics nor TENS was delivered. To evaluate hyperalgesia, paw withdrawal latency (PWL) to radiant heat was measured before nerve constriction and five times after the constriction; just before TENS and at 1, 3, 7, and 14 days after the completion of TENS. Compared to the non-TENS groups, rats in the TENS groups showed significantly reduced thermal hyperalgesia at least for 3 days (Pent-TENS group) or for 7 days (Hal-TENS group) after TENS. These results indicate a possible long-lasting therapeutic effect of TENS applied under general anesthesia.