RESUMO
Na(+)-K(+)-ATPase pump failure during either anoxia or ouabain perfusion induces rapid axonal depolarization by dissipating ionic gradients. In this study, we examined the interplay between cation and anion transporting pathways mediating axonal depolarization during anoxia or selective Na(+)-K(+)-ATPase inhibition. Compound resting membrane (V(m)) potential of rat optic nerve was measured in a grease gap at 37 degrees C. Chemical anoxia (2 mM NaCN or NaN(3)) or ouabain (1 mM) caused a loss of resting potential to 42 +/- 11% and 47 +/- 2% of control after 30 min, respectively. Voltage-gated Na(+)-channel blockade was partially effective in abolishing this depolarization. TTX (1 microM) reduced depolarization to 73 +/- 10% (chemical anoxia) and 68 +/- 4% (ouabain) of control. Quaternary amine Na(+) channel blockers QX-314 (1 mM) or prajmaline (100 microM) produced similar results. Residual ionic rundown largely representing co-efflux of K(+) and Cl(-) during chemical anoxia in the presence of Na(+)-channel blockade was further spared with DIDS (500 microM), a broad-spectrum anion transport inhibitor (95 +/- 8% of control after 30 min in anoxia + TTX vs. 73 +/- 10% in TTX alone). Addition of DIDS was slightly more effective than TTX alone in ouabain (74 +/- 5% DIDS + TTX vs. 68 +/- 4% in TTX alone, P < 0.05). Additional Na(+)-entry pathways such as the Na-K-Cl cotransporter were examined using bumetanide, which produced a modest albeit significant sparing of V(m) during ouabain-induced depolarization. Although cation-transporting pathways play the more important role in mediating pathological depolarization of central axons, anion-coupled transporters also contribute to a significant, albeit more minor, degree.
Assuntos
Inibidores Enzimáticos/farmacologia , Glicólise/efeitos dos fármacos , Hipóxia/fisiopatologia , Nervo Óptico/efeitos dos fármacos , Nervo Óptico/fisiologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Animais , Bumetanida/farmacologia , Cloretos/metabolismo , Cloretos/fisiologia , Diuréticos/farmacologia , Hipóxia/induzido quimicamente , Iodoacetatos/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Ouabaína/farmacologia , Ratos , Ratos Long-Evans , Sódio/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Tetrodotoxina/farmacologiaRESUMO
Twenty-six patients with cervical spondylosis and radiculomyelopathy were treated surgically. Eight patients had cervical laminectomy C1--C7, and 16 patients had complete cervical laminectomy C1--C7 with excision of the posterior rim of the foramen magnum. Follow-up of patients was from two months to eight years. The majority of patients improved markedly, and some of them had excellent results.