Methods: Using a combination of the patch clamp technique and the entire soma isolation method, the action of meperidine on voltage-gated Na+ and K+ currents in spinal dorsal horn neurons of rats was described. Current clamp recordings from intact neurons showed the functional relevance of the ion current blockade for the generation of action potentials.
Results: Externally applied meperidine reversibly blocked voltage-gated Na+ currents with a half-maximum inhibiting concentration (IC50) of 112 [mu]m. During repetitive stimulation, a slight phasic block occurred. In addition, A-type K+ currents and delayed-rectifier K+ currents were affected in a dose-dependent manner, with IC50 values of 102 and 52 [mu]m, respectively. In the current clamp mode, single action potentials were suppressed by meperidine. The firing frequency was lowered to 54% at concentrations (100 [mu]m) insufficient for the suppression of a single action potential. 相似文献
Methods: Using a combination of the whole-cell patch-clamp recording from spinal cord slices and the entire soma isolation method, we studied the direct action of droperidol on two types of Na+ currents in dorsal horn neurons of young rats.
Results: The tetrodotoxin-sensitive Na+ current in isolated somata consisted of a fast inactivating ([tau]F, 0.5-2 ms; 80-90% of the total amplitude) and a slow inactivating ([tau]S, 6-20 ms; 10-20% of the total amplitude) component. Droperidol, at concentrations relevant for spinal and epidural anesthesia, selectively and reversibly suppressed the fast component with a half-maximum inhibiting concentration (IC50) of 8.3 [mu]m. The slow inactivating component was much less sensitive to droperidol; the estimated IC50 value was 809 [mu]m. 相似文献
Methods: The baseline H reflex and F wave were measured before anesthesia in 15 adult patients. After induction, 1% end-tidal isoflurane was maintained for 20 min before the H and F waves were reelicited. Using an electric stimulus applied to the forearm and grading the response as movement or no movement, the authors increased or decreased the isoflurane concentration in 0.1% steps, depending on the movement responses. The H and F waves were recorded 20 min after each change of isoflurane concentration. The correlation between H- and F-wave suppression and surgical immobility was analyzed using a paired t test with Bonferroni correction.
Results: H-reflex amplitude (2.74 +/- 1.63 mV) and F-wave persistence (70.69 +/- 26.19%) at the highest isoflurane concentration that allowed movement response to a stimulus are different (P < 0.01) from these (1.97 +/- 1.46 mV; 43.16 +/- 22.91%) at the lowest isoflurane concentration that suppressed response. At 0.8% isoflurane, the H-reflex amplitude was 3.69 +/- 1.83 mV with movement and 1.01 +/- 1.14 mV without movement (P < 0.01); F-wave amplitude was 0.29 +/- 0.15 mV with movement and 0.11 +/- 0.06 mV without movement (P < 0.01); F-wave persistence was 80 +/- 22.36% with movement and 34.9 +/- 25.75% without movement (P < 0.01). 相似文献
Methods: The authors used whole cell patch clamp in acutely isolated small-diameter neurons to determine how localized inflammation (3-5 days) of L4 and L5 ganglia altered voltage-gated K+ and Na+ currents.
Results: Tetrodotoxin-sensitive Na+ currents increased twofold to threefold in neurons from inflamed ganglia. Tetrodotoxin-resistant Na+ currents increased more than twofold, but only in cells that bound isolectin B4. These increases occurred without shifts in voltage dependence of activation and inactivation. Similar results are seen in models of peripheral inflammation, except for the large magnitudes. Unlike most pain models, localized inflammation increased rather than decreased voltage-gated K+ currents, due to increased amplitudes of the sustained (delayed rectifier) and fast-inactivating transient components. The overall effect in current clamp experiments was an increase in excitability as indicated by decreased rheobase and lower action potential threshold. 相似文献
Methods: Neuromuscular transmission was studied using a two-electrode voltage clamp, with isoflurane applied in physiologic saline. The relation between ionic conductances and presynaptic function was modeled in the Neuron Simulation Environment. Motoneuron ionic currents were monitored via whole cell recordings.
Results: Presynaptic inhibition by isoflurane was enhanced significantly in para mutants. Computer simulations of presynaptic actions of anesthetics indicated that each candidate target conductance would have diagnostic effects on the relation between latency and amplitude of synaptic currents. The experimental latency-amplitude relation for isoflurane most closely resembled activation of a simulated hyperpolarizing leak. Simulations indicated that increased isoflurane potency in para axons resulted from reduced excitability of mutant axons. In whole cell recordings, isoflurane activated a hyperpolarizing leak current. The effects of isoflurane at the neuromuscular junction were insensitive to low pH. 相似文献
Methods: Responses of single spinal neurons were recorded in instrumented sheep that were untrained and free from drugs or recent surgery, in either fully conscious or halothane-anesthetized states. Receptive field (RF) size was measured before and after non-noxious mechanical conditioning stimulation.
Results: Noxious conditioning stimuli in anesthetized sheep caused enlargement of RF areas, as expected. Conditioning with nonpainful scratching or other stimuli was without effect in anesthetized animals; in marked contrast, it caused enlargement of RF size in conscious animals, in which 29 of 33 wide dynamic range units but only 1 of 12 low-threshold mechanoreceptive neurons were affected. 相似文献
Methods: The effects of a clinically relevant concentration (1 rat minimum alveolar concentration [MAC]) of isoflurane on electrically evoked and spontaneous excitatory/inhibitory transmission and on the response to exogenous administration of the [gamma]-aminobutyric acid type A receptor agonist muscimol were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique. The effect of isoflurane on the action potential-generating membrane property was also examined.
Results: Bath-applied isoflurane (1.5%, 1 rat MAC) diminished dorsal root-evoked polysynaptic but not monosynaptic excitatory postsynaptic currents. Glutamatergic miniature excitatory postsynaptic currents were also unaffected by isoflurane. In contrast, isoflurane prolonged the decay phase of evoked and miniature [gamma]-aminobutyric acid type A receptor-mediated inhibitory postsynaptic currents and increased the amplitude of the muscimol-induced current. Isoflurane had little effect on action potential discharge activity. 相似文献
Methods: Six volunteers received lidocaine spinal anesthesia with 50 mg lidocaine (5% in dextrose). Cutaneous current perception thresholds at 2,000, 250, and 5 Hz, which stimulate A beta, A delta, and C fibers, respectively, were determined at L2-L3 (medial aspect above knee) before and every 10 min after spinal anesthesia. Dermatomal levels to pinprick, touch, and cold were assessed every 5 min after spinal anesthesia. Tolerance to tetanic electrical stimulus was assessed at L2-L3 every 10 min after spinal anesthesia.
Results: Differential block was demonstrated by the sequential return of sensation to touch, pinprick, and cold at L2-L3. Recovery of function of A beta, A delta, and C fibers correlated with return of sensation to touch (R2 = 0.7, p = 0.03), pinprick (R2 = 0.75, p = 0.02), and cold (R2 = 0.67, p = 0.04) respectively. Loss of tolerance of surgical anesthesia corresponded to return of A beta current perception thresholds to baseline, whereas current perception thresholds for A delta and C fibers were still increased to greater than baseline (p = 0.025). 相似文献
Methods: This study uses pharmacological methods to isolate LVACC in cells from the dorsal root ganglia of neuropathic and sham-operated rats, including the blockade of high-voltage-activated Ca channels with fluoride and selective toxins. LVACCs were examined with conventional whole cell patch clamp electrophysiology techniques.
Results: After chronic constriction injury of the peripheral axon, LVACC was significantly reduced compared to sham rats as shown by a 60% reduction in peak current density and an 80% reduction in total calcium influx. A depolarizing shift in the voltage dependence of activation and an increase in the rate of deactivation and inactivation appear to cause this reduction of LVACC. Either Ni2+ or mibefradil, blockers of LVACC, applied in the bath to normal dorsal root ganglion cells during current clamp significantly and reversibly increased excitability. 相似文献
Methods: Resting [Ca2+]c was determined by microfluorometry in Fura-2 AM-loaded neurons dissociated from dorsal root ganglia of animals with hyperalgesia to mechanical stimulation after spinal nerve ligation and section (SNL) at the fifth and sixth lumbar (L5 and L6) levels and from animals after skin incision alone (control group). Axotomized neurons from the L5 dorsal root ganglia were examined separately from adjacent L4 neurons that share the sciatic nerve with degenerating L5 fibers.
Results: After SNL, large (34 [mu]m or larger) neurons from the L4 ganglion showed a 29% decrease in resting [Ca2+]c, whereas those from the L5 ganglion showed a 54% decrease. Small neurons only showed an effect of injury in the axotomized L5 neurons, in which resting [Ca2+]c decreased by 30%. A decrease in resting [Ca2+]c was not seen in neurons isolated from rats in which hyperalgesia did not develop after SNL. In separate experiments, SNL reduced resting [Ca2+]c in capsaicin-insensitive neurons of the L5 ganglion by 60%, but there was no change in neurons from L4. Resting [Ca2+]c of capsaicin-sensitive neurons was not affected by injury in either ganglion. SNL injury decreased the proportion of neurons sensitive to capsaicin in the L5 group but increased the proportion in the L4 group. 相似文献
Methods: The effects of midazolam on electrically evoked and spontaneous excitatory transmission were examined in lamina II neurons of adult rat spinal cord slices using the whole cell patch clamp technique.
Results: Bath-applied midazolam (1 [mu]m) diminished A[delta]- and C-fiber evoked polysynaptic excitatory postsynaptic currents in both amplitude and integrated area. However, it affected neither A[delta]- and C-fiber evoked monosynaptic excitatory postsynaptic currents in amplitude nor miniature excitatory postsynaptic currents in amplitude, frequency, and decay time constant. In the presence of a benzodiazepine receptor antagonist, flumazenil (5 [mu]m), midazolam (1 [mu]m) did not diminish A[delta]-fiber evoked polysynaptic excitatory postsynaptic currents, suggesting that midazolam modulate the [gamma]-aminobutyric acid interneurons in the dorsal horn. 相似文献