The cytosolic free calcium concentration ([Ca2+]i) isolated from the cochlear outer hair cell (OHC) of the guinea pig was measured using microfluorimetric imaging technique and the effects of free radicals were investigated. Hypoxanthine (HX) plus xanthine oxidase (XO) induced a rise in [Ca2+]i in the presence of external Ca2+. Elimination of external Ca2+ (pCa = 7) did not show an increase in [Ca2+i, indicating that the increased [Ca2+]i is dependent on external Ca2+. The elevation of [Ca2+]i induced by HX-XO was reduced by addition of superoxide dismutase or nifedipine but not by addition of catalase. A single admission of HX or XO failed to affect [Ca2+]i. These findings suggest that superoxide anion generated in the OHC increases the Ca2+ influx across the membrane, presumably leading to some pathological changes in the acoustic transduction by modulating the OHC motility.
Endoscopic sinus surgery (ESS) was compared with Caldwell-Luc (C-L) operation based on blood loss during surgery, operation time, period of hospitalization and complications. Both blood loss and operation time were significantly reduced in ESS as compared with C-L operation. In addition, patients undergoing ESS resulted in discharges after surgery earlier than those undergoing C-L operation. Minor complication was seen in 4.8% of the ESS patients whereas no major complication was recognized. ESS is a relatively safe procedure with superiority over C-L operation.
Vestibular dark cells (VDC) are known to electrogenically secrete K+ via slowly activating K+(IsK) channels, consisting of IsK regulatory and KvLQT1 channel subunits, and the associated short-circuit current ( I sc) is inhibited by agonists of the apical P2U(P2Y2) receptor (J. Liu, K. Kozakura, and D. C. Marcus. Audit. Neurosci. 2: 331–340, 1995). Measurements of relative K+ flux ( J K) with a self-referencing K+-selective probe demonstrated a decrease in J K after apical perfusion of 100 μM ATP. On-cell macropatch recordings from gerbil VDC showed a decrease of the IsKchannel current ( I IsK) by 83 ± 7% during pipette perfusion of 10 μM ATP. The magnitude of the decrease of I scby ATP was diminished in the presence of inhibitors of phospholipase C (PLC) and protein kinase C (PKC), U-73122 and GF109203X. Activation of PKC by phorbol 12-myristate 13-acetate (PMA, 20 nM) decreased I IsK by 79 ± 3% in perforated-patch whole cell recordings, whereas the inactive analog, 4α-PMA, had no effect. In contrast, elevation of cytosolic Ca2+ concentration by A-23187 increased the whole cell I IsK . The expression of the isk gene transcript was confirmed, and the serine responsible for the species-specific response to PKC was found to be present in the gerbil IsKsequence. These data provide evidence consistent with a direct effect of the PKC branch of the PLC pathway on the IsK channel of VDC in response to activation of the apical P2Ureceptor and predict that the secretion of endolymph in the human vestibular system may be controlled by PKC in the same way as in our animal model.
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