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KMID : 0811720070110000078
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Korean Journal of Physiology & Pharmacology
2007 Volume.11 No. 0 p.78 ~ p.0
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An Important Role of NKCC in Generating GABA-elicited Calcium Transients in the Suprachiasmatic Nucleus (SCN) Neurons
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Choi Hee-J
Kim Yoon-Sik
Lee Chang-Joon Justin
Kim Woong-Bin
Kim Yang-In
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Abstract
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The locus of mammalian circadian pacemaker SCN consists of GABAergic neurons, and ~50% of synapses in this nucleus are GABAergic. A recent study showed that a significant proportion of neurons in the adult rat SCN exhibited depolarizing, excitatory GABAA receptor-mediated postsynaptic potentials (GPSPs) when recorded during the night phase, and a more recent study from this laboratory (Choi et al., 2003) indicated that the emergence of the excitatory GPSPs relies on NKCC (Na+-K+-2Cl－ cotransporter) that accumulates chloride intracellularly. Also, from some calcium imaging experiments (Choi et al., 2006), we obtained results that about 40% of SCN neurons recorded during the projected night showed an increase in calcium level in response to GABA, and the NKCC blocker bumetanide (10 μM) reduced the calcium response. These results indicate that intracellular chloride accumulation by NKCC is prerequisite to the GABA-elicited calcium increase. In the current study, to obtain further evidence for this hypothesis, we conducted more calcium imaging experiments using NKCC1 knockout mice. The proportion of neurons showing calcium transients in response to GABA was much smaller in mutant than wild-type mice [27 of 494 cells (5.5%) vs. 114 of 531 cells (21.5%); p＜0.001]. Moreover, the GABA-evoked calcium transients in mutant were lower in amplitude (NKCC1+/+: 0.70±0.08 F340/F380, n=114; NKCC1-/-: 0.32±0.03, n=27, p＜0.02). The infrequent, low-amplitude GABA-elicited calcium transients in NKCC1-/- mice were insensitive to bumetanide, whereas those from wild-type mice were significantly reduced by bumetanide (50.6±8.3% of control, n=24; p=0.0003). The present results support the hypothesis that NKCC is responsible for GABA-elicited calcium increase in SCN neurons. In addition, coupled with the results of our earlier study (Choi et al., 2003 & 2006), they point to the possibility that excitatory GPSPs are a driving force for intracellular calcium rise in SCN neurons.
Source: Korean Journal of Physiology & Pharmacology.2007 Oct;11(Suppl II):S77-S77
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KEYWORD
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SCN, GABA, NKCC1, Bumetanide
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