Role of endolymphatic anion transport in forskolin-induced Cl- activity increase of scala media.
To determine the role of anion transport in the forskolin-induced Cl- increase of scala media (SM), effects of forskolin on the EP (endocochlear potential) and Cl- activity (ACl) in SM were examined with double-barrelled Cl(-)-selective microelectrodes. The experiments were carried out on guinea pig cochleae, using a few anion transport inhibitors: IAA-94 for a Cl- channel blocker, bumetanide (BU) for an Na+/K+/2Cl- cotransport blocker, and SITS and DIDS for Cl-/HCO3- exchange blockers. The application of forskolin (200 microM) into scala vestibuli (SV) caused a 20 mEq increase of endolymphatic ACl and a 15 mV elevation of EP, and IAA-94 with forskolin completely abolished these responses. Although each application of BU, SITS or DIDS did not completely suppress EP elevation, the concurrent application of these inhibitors completely suppressed EP with endolymphatic ACl increase. The results indicate the involvement of Cl- channels, Na+/K+/2Cl- cotransport and Cl-/HCO3- exchange in forskolin-induced increase of ACl and EP. The role of adenylate cyclase activation and Cl- transport in endolymph homeostasis was discussed.
Kitano
I
I
Department of Otolaryngology, Nara Medical University, Japan.
Mori
N
N
Matsunaga
T
T
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D003053:Cochlear Duct / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D004710:Endolymph / Q000187:drug effects / Q000378:metabolism; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D006016:Glycolates / Q000494:pharmacology; D006168:Guinea Pigs; D006706:Homeostasis; D017136:Ion Transport / Q000187:drug effects; D008839:Microelectrodes
D001639:Bicarbonates; D002712:Chlorides; D006016:Glycolates; D002034:Bumetanide; D005576:Colforsin; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C015765:MK 473; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid