Decreased Immunoreactivities and Functions of the Chloride Transporters, KCC2 and NKCC1, in the Lateral Superior Olive Neurons of Circling Mice

Jonu Pradhan; Dhiraj Maskey; 박기섭; 김명주; 안승철

추천

검색

자료유형: 학술저널

저자정보: Jonu Pradhan Dhiraj Maskey 박기섭 김명주 안승철

저널정보: 대한이비인후과학회 Clinical and Experimental Otorhinolaryngology Clinical and Experimental Otorhinolaryngology 제4권 제1호

발행연도: 2011.1

수록면: 18 - 23 (6page)

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Objectives. We tested the possibility of differential expression and function of the potassium-chloride (KCC2) and sodiumpotassium-2 chloride (NKCC1) co-transporters in the lateral superior olive (LSO) of heterozygous (+/cir) or homozygous (cir/cir) mice. Methods. Mice pups aged from postnatal (P) day 9 to 16 were used. Tails from mice were cut for DNA typing. For Immunohistochemical analysis, rabbit polyclonal anti-KCC2 or rabbit polyclonal anti-NKCC1 was used and the density of immunolabelings was evaluated using the NIH image program. For functional analysis, whole cell voltage clamp technique was used in brain stem slices and the changes of reversal potentials were evaluated at various membrane potentials. Results. Immunohistochemical analysis revealed both KCC2 and NKCC1 immunoreactivities were more prominent in heterozygous (+/cir) than homozygous (cir/cir) mice on P day 16. In P9–P12 heterozygous (+/cir) mice, the reversal potential (Egly) of glycine-induced currents was shifted to a more negative potential by 50 μM bumetanide, a known NKCC1 blocker, and the negatively shifted Egly was restored by additional application of 1 mM furosemide, a KCC2blocker (-58.9±2.6 mV to -66.0±1.5 mV [bumetanide], -66.0±1.5 mV to -59.8±2.8 mV [furosemide+bumetanide],n=11). However, only bumetanide was weakly, but significantly effective (-60.1±2.9 mV to -62.7±2.6 mV [bumetanide],-62.7±2.6 mV to -62.1±2.5 mV [furosemide+bumetanide], n=7) in P9–P12 homozygous (cir/cir) mice. Conclusion. The less prominent immunoreactivities and weak or absent responses to bumetanide or furosemide suggest impaired function or delayed development of both transporters in homozygous (cir/cir) mice.

#Potassium-chloride co-transporter #Sodium-potassium-2 chloride co-transporter #Lateral superior olive #Circling mice

참고문헌 (33)

참고문헌 신청

Friauf E / 2008 / Hypothyroidism impairs chloride homeostasis and onset of inhibitory neurotransmission in developing auditory brainstem and hippocampal neurons / Eur J Neurosci 28(12):2371~2380

Kakazu Y / 1999 / Regulation of intracellular chloride by cotransporters in developing lateral superior olive neurons / J Neurosci 19(8):2843~2851

de Jong JC / 2003 / The structural unit of the thiazide-sensitive NaCl cotransporter is a homodimer / J Biol Chem 278(27):24302~24307

Moore-Hoon ML / 2000 / The structural unit of the secretory Na+-K+-2Cl-cotransporter (NKCC1) is a homodimer / Biochemistry 39(13):3718~3724

Blaesse P / 2006 / Oligomerization of KCC2 correlates with development of inhibitory neurotransmission / J Neurosci 26(41):10407~10419