2002 Fiscal Year Final Research Report Summary
Cell physiological and molecular biological mechanisms of the function of the stria vascularis in the cochlea
| Project/Area Number |
12671671
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kochi Medical School |
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Principal Investigator |
TAKEUCHI Shunji Kochi Medical School, Otolaryngology, Associate Professor, 医学部, 助教授 (50188158)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIGI Akinobu Kochi Medical School, Otolaryngology, Assistant Professor, 医学部, 講師 (60243820)
ANDO Motonori Kochi Medical School, Physiology, Research Associate, 医学部, 助手 (20222789)
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| Project Period (FY) |
2000 – 2002
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| Keywords | stria vascularis / melanocyte / potassium channel / Na-K-Cl cotransporter / endocochlear potential / amiloride / intercellular space / loop diuretics |
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| Research Abstract |
Intermediate cells are melanocytes in the stria vascularis. To examine the contribution of the membrane potential of intermediate cells (E_m) to the endocochlear potential (EP), a comparison was made between the effects of K^+ channel blockers on the E_m and those on the EP. The E_m changed by 55.1 mV per ten-fold changes in extracellular K^+ concentration. Ba^<2+>, Cs^+ and quinine depressed the E_m in a dose-dependent manner, whereas tetraethylammonium at 30 mM and 4-aminopyridine at 10 mM had no effect. To examine the effect of the K^+ channel blockers on the EP, the EP of guinea pigs was maintained by vascular perfusion, and K^+ channel blockers were administered to the artificial blood. Ba^<2+>, Cs^+ and quinine depressed the EP in a dose-dependent manner, whereas tetraethylammonium at 30 mM and 4-aminopyridine at 10 mM did not change the EP. The changes in the EP were similar to those seen in the E_m On the basis of these results, we propose that : the EP is critically dependent
… More
on the voltage jump across the plasma membrane of intermediate cells.
The intercellular space in the stria vascularis (intrastrial space) is a closed space and isolated from both the endolymph and the perilymph in normal tissue. Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space in association with a decline in the endocochlear potential. It is known that bumetanide inhibits the Na^+-K^+-2Cl^- cotransporter, which is expressed abundantly in the basolateral membrane of marginal cells. We studied ionic mechanisms underlying the bumetanide-induced enlargement of the intrastrial space using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with artificial perilymph containing 100 μM bumetanide caused marked enlargement of the intrastrial space, as reported previously. Removal of K^+ from the perilymph did not affect the bumetanide-induced enlargement, whereas removal of Na^+ from the perilymph inhibited it almost completely. Perilymph containing 1 mM amiloride also inhibited the enlargement of the intrastrial space almost completely. These results indicate that perilymphatic Na^+, but not K^+, and amiloride-sensitive pathways are essential to the bumetanide-induced enlargement of the intrastrial space. Two possible pathways could yield these results. Na^+ in the perilymph could enter the endolymph via Reissner's membrane or the basilar membrane ; Na^+ in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na^+-K^+-ATPase in the basolateral membrane of them. Another, less likely, possibility is that Na^+ in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na^+-K^+-ATPase of intermediate cells. Less
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