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Biomedical subjects

Shumei Shibata

Publications and source records attributed to Shumei Shibata.

5 recordsLinked to original sources

Bilirubin potentiates inhibitory synaptic transmission in lateral superior olive neurons of the rat.

Bilirubin is a well-known neurotoxin that can result in multiple neurologic deficits. Previous studies have suggested that bilirubin affects aspects of synaptic transmission; however the acute effects of bilirubin on synaptic transmission have not been examined in real-time. In this study, using whole-cell voltage-clamp recordings, we observed the effect of bilirubin on inhibitory postsynaptic currents (IPSC) in postnatal 13-15-day-old neurons dissociated from lateral superior olive nuclei (LSO), one of the brainstem auditory nucleus that are highly vulnerable to bilirubin. The results showed that 10(-5)M bilirubin increased the frequency of spontaneous IPSC without causing change in their amplitudes or in the response to bath applied glycine, suggesting a presynaptic locus for the action. In the presence of tetrodotoxin, the frequency of miniature IPSC was also potentiated by 10(-5)M bilirubin. The facilitation by bilirubin was concentration dependent and increased with an increase in exposure time. Bicuculline only partially reduced the action of bilirubin. The action of bilirubin was observed in extracellular Ca(2+)-free ([Ca(2+)](o) free) solution but was fully occluded by pretreatment with BAPTA-AM in [Ca(2+)](o) free solution. Thus, in LSO neurons, bilirubin facilitates inhibitory synaptic transmission, in a manner independent of voltage-activated Na(+) and Ca(2+) channels but dependent on presynaptic [Ca(2+)](i). The increase of inhibitory synaptic transmission in response to acute bilirubin is a novel effect of bilirubin on the central nervous system and may have implications for neurotoxicity and the impairment of auditory transduction seen in hyperbilirubinemia.

Animals↗

Squamous cell carcinoma of the external auditory canal and middle ear: an operation combined with preoperative chemoradiotherapy and a free surgical margin.

OBJECTIVE: Treatment outcomes for squamous cell carcinoma of the temporal bone were evaluated regarding stage, therapeutic strategy, and prognostic factors. STUDY DESIGN: Retrospective case review. SETTING: University hospital and outpatient clinic. PATIENTS: Twenty-five patients with primary squamous cell carcinoma of the external auditory canal and middle ear. INTERVENTION: Preoperative chemoradiotherapy and radiotherapy were used in 7 of 12 patients. Lateral temporal bone resection was performed for the lesions not beyond the tympanic membrane. Subtotal temporal bone resection was chosen for lesions extending to the middle ear cavity when there was no invasion to the pyramidal apex, carotid canal, or dura or metastasis. Others were conservatively treated by chemoradiotherapy. When the performance status was poor or an agreement regarding the operation could not be reached, the treatment was modified. MAIN OUTCOME MEASURE: Estimated survival rates. RESULTS: The 3-year estimated survival for T1 and T2 lesions was 100%. The 5-year estimated survival for T3 and T4 lesions was 80% and 35%, respectively. The 5-year estimated survival improved up to 75% for T4 tumors with operation and 16% for those without operation after 47 months. The tumor-free surgical margin is significantly related to patient survival in T3 and T4 lesions. Multivariate analysis predicted that concomitant chronic otitis media and positive lymph nodes were significantly associated with poorer survival. CONCLUSION: The tumor-free surgical margin was important to survival. When T4 lesions did not involve the pyramidal apex, carotid canal, dura, or any lymph nodes, the surgical intervention improved the estimated survival rate to a level as good as T3 lesions.

Adult↗

GABA-induced response in spiral ganglion cells acutely isolated from guinea pig cochlea.

The physiological and pharmacological properties of gamma-aminobutyric acid (GABA)-induced responses were investigated in acutely isolated spiral ganglion cells (SGCs) of guinea pig by using either a nystatin-perforated patch recording configuration or a conventional whole-cell patch recording mode combined with rapid drug application. GABA and GABA(A) subtype receptor agonist, muscimol, induced inward currents in a concentration-dependent manner in 74% of all cells. The current-voltage relationship for the GABA response indicated the GABA-induced current in SGCs is carried by Cl-. Bicuculline (BIC), strychnine (STR), and picrotoxin (PTX) suppressed the GABA response in a concentration-dependent manner. BIC and STR, and PTX blocked the GABA response in a competitive manner and in a non-competitive manner, respectively. For inorganic antagonists, Cd2+ and Ni2+ also inhibited the GABA response. On the other hand, Zn2+ failed to suppress the GABA response in SGCs. An antibiotic, benzylpenicillin, suppressed the GABA response. The GABA response was augmented by both a barbiturate derivative, pentobarbital (PB), and a benzodiazepine derivative, diazepam. The results suggest clearly that the physiological and pharmacological characteristics of GABA(A) receptor on acutely isolated guinea pig SGCs are quite similar to the common GABA(A) receptor found in other sensory ganglion cells.

Animals↗

Experience-dependent changes in intracellular Cl- regulation in developing auditory neurons.

A developmental change in GABA and glycine responses, from a depolarization to a hyperpolarization, have been reported for a range of CNS neurons, and has been demonstrated to be due to a developmental decrease in the intracellular Cl- concentration ([Cl-](i)). We examined [Cl-](i) in isolated rat lateral superior olive (LSO) neurons using patch-clamp recordings of glycine gated Cl- currents and by measuring intracellular Cl- -fluorescence. In neurons from 14-16-day-old rats (P14-P16), which had previously received unilateral or bilateral cochlear ablations before the onset of hearing, there was no developmental decrease in [Cl-](i). No significant differences in [Cl-](i) were observed amongst rats with either ipsi- and contralateral ablations. Implanted strychnine pellets also prevented the decrease in [Cl-](i) in most neurons. In some of these neurons in which [Cl-](i) remained high, there was a lack of expression of the K+-Cl- cotransporter 2 (KCC2) mRNA. These results demonstrate that the developmental decrease in [Cl-](i) in LSO neurons is dependent on neuronal activity and that both GABAergic/glycinergic and glutamatergic afferent activity contribute to this maturation of the Cl- regulatory mechanisms.

Acoustic Stimulation↗

Developmental switch from GABA to glycine release in single central synaptic terminals.

Early in postnatal development, inhibitory inputs to rat lateral superior olive (LSO) neurons change from releasing predominantly GABA to releasing predominantly glycine into the synapse. Here we show that spontaneous miniature inhibitory postsynaptic currents (mIPSCs) also change from GABAergic to glycinergic over the first two postnatal weeks. Many 'mixed' mIPSCs, resulting from co-release of glycine and GABA from the same vesicles, are seen during this transition. Immunohistochemistry showed that a large number of terminals contained both GABA and glycine at postnatal day 8 (P8). By P14, both the content of GABA in these mixed terminals and the contribution of GABA to the mixed mIPSCs had decreased. The content of glycine in terminals increased over the same period. Our results indicate that switching from GABAergic to glycinergic inputs to the LSO may occur at the level of a single presynaptic terminal. This demonstrates a new form of developmental plasticity at the level of a single central synapse.

Animals↗