RESUMO
Activity-dependent changes of synaptic efficacy in the superior cervical ganglion (SCG) can be prevented by gamma-aminobutyric acid (GABA). We have studied the effects of picrotoxin (PTX) on GABA-mediated inhibition of long-term potentiation (LTP) of synaptic transmission in the rat SCG. Compound action potentials were recorded extracellularly in the postganglionic internal carotid nerve in response to preganglionic nerve stimulation. PTX (100 microM) antagonized the inhibition by exogenous GABA (250 microM) of LTP induced by strong tetanic stimulation (20 Hz, 20s, supramaximal stimulation, partial blockade of transmission by hexamethonium). Additionally, PTX alone (50 microM) facilitated the induction of LTP by a weak tetanus (20 Hz, 5 s, submaximal stimulation). These results further support previous data indicating that activation of GABAA-like receptors can prevent the occurrence of synaptic plasticity at this peripheral synapse.
Assuntos
Antagonistas GABAérgicos/farmacologia , Plasticidade Neuronal/efeitos dos fármacos , Picrotoxina/farmacologia , Gânglio Cervical Superior/fisiologia , Ácido gama-Aminobutírico/farmacologia , Animais , Eletrofisiologia , Agonistas de Receptores de GABA-A , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Ratos , Ratos Wistar , Receptores de GABA-A/fisiologia , Gânglio Cervical Superior/química , Gânglio Cervical Superior/efeitos dos fármacosRESUMO
We have compared the effect of calcium channel blockers on the potassium-evoked release of tritium-labeled acetylcholine and on preganglionic spike-evoked synaptic transmission in the rat superior cervical ganglion. Transmitter release at the nerve terminals is mediated by the influx of calcium through voltage-gated calcium channels. While four types of voltage-gated calcium channels (T, L, N and P) have been identified in neurons, it is not clear which may actually be involved in excitation-secretion coupling. Release of tritiated acetylcholine evoked by sustained depolarization in high (40 mM) extracellular potassium decreased markedly in the absence of calcium or the presence of cadmium. High potassium-evoked release was substantially inhibited by the P-type channel blockers, purified from funnel-web spider toxin, and omega-agatoxin-IVA, and by the N-type channel blocker omega-conotoxin-GVIA, but was unaffected by the L-type channel blocker nitrendipine. In contrast, postganglionic compound action potentials synaptically triggered by preganglionic stimulation were strongly blocked by funnel-web spider toxin and slightly blocked by a high concentration of omega-agatoxin-IVA, but were unaffected by either omega-conotoxin-GVIA, nitrendipine or a low concentration of omega-agatoxin-IVA. Thus, at the superior cervical ganglion, funnel-web spider toxin-sensitive calcium channels play a dominant role in transmitter release evoked by transient, spike-mediated depolarization, but other types of voltage-gated calcium channels in addition to the funnel-web spider toxin-sensitive channel mediate the transmitter release that is evoked by sustained high potassium depolarization.
Assuntos
Acetilcolina/metabolismo , Potenciais de Ação/efeitos dos fármacos , Canais de Cálcio/fisiologia , Gânglios Simpáticos/fisiologia , Animais , Arginina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Poliaminas/farmacologia , Ratos , Ratos Wistar , Espermidina/farmacologiaRESUMO
The effect of gamma-aminobutyric acid (GABA) on synaptic transmission in rat superior cervical ganglion (SCG) was assessed in vitro by extracellular recording. Postganglionic compound action potentials (CAPs) triggered by preganglionic stimulation were blocked in a reversible and concentration-dependent fashion by short, 60 s long, superfusion with GABA (IC50 = 39.3 microM), with the GABAA agonist muscimol (IC50 = 8.7 microM) or with the GABAB agonist baclofen (IC50 = 145 microM). Responses to GABA and muscimol, but not to baclofen, exhibited desensitization after 5 min long superfusions with the drugs. In a long-term potentiation (LTP) paradigm, the degree of potentiation found 30 min after a tetanic train of stimuli (20 Hz for 20 s) was strongly inhibited by GABA (100-250 microM), when superfused at the time of tetanic stimulus or shortly thereafter. The effect of GABA on SCG LTP was mimicked by muscimol but not by baclofen. The results are compatible with the view that GABA exerts overall inhibitory effects in rat SCG, including transmission blockade of single impulses (through activation of GABAA and GABAB receptors) and impairment of activity-dependent potentiation of nicotinic transmission (through activation of GABAA receptors).
Assuntos
Gânglios Simpáticos/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Receptores Nicotínicos/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Ácido gama-Aminobutírico/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Baclofeno/farmacologia , Estimulação Elétrica , Masculino , Muscimol/farmacologia , Ratos , Ratos WistarRESUMO
The properties of singles K+ channels in normal and denervated muscles were compared using the "patch-clamp" technique. Single channels were recorded from vesicles obtained by stretching bundles of normal and denervated extensor digitorium longus (EDL) muscles. The most frequently observed channel in normal muscles was a high conductance (266 pS) Ca++ activated K+ channel. Although channel density, as estimated by patch recording, showed a significant decrease in denervated muscles, no differences were found in conductance and gating properties. Another voltage-dependent K+ channel (81 pS) was only recorded from normal muscles, but never from denervated ones. In addition, a 35 pS conductance was recorded from both normal and denervated fibers. This channel displayed neither voltage dependence nor sensitivity to tetraethylammonium (TEA). In contrast, another TEA-insensitive (16 pS) channel was recorded only from denervated muscles. We conclude that denervation induces significant changes in the distribution and expression of K+ channels in mammalian skeletal muscles.