Murai Yoshinaka, Akaike Tadashi
Department of Oral Functional Science (Physiology), Graduate School of Dental Medicine, Hokkaido University, Kita 13 Nishi 7, Kita-ku, Sapporo 060-8586, Japan.
Neurosci Res. 2005 Jan;51(1):55-65. doi: 10.1016/j.neures.2004.09.005.
The locus coeruleus (LC) contains noradrenergic neurons that are innervated by orexin (ORX)-like immunoreactive axons and express both orexin receptor-1 and -2. We studied effects of ORX-A and -B (ORX-A/B) on dissociated LC neurons by using whole-cell patch clamp techniques. In current-clamp mode, LC neurons were depolarized by application of ORX-A (10(-7) M) [53% of neurons tested; 9.0+/-0.2 mV (n=5)], or ORX-B (10(-7) M) [38% of neurons tested; 4.0+/-0.1 mV (n=5)]. Firing frequencies of action potentials increased during application [1.1+/-0.2 Hz (n=5) in ORX-A; 0.8+/-0.2 Hz (n=5) in ORX-B] and returned to the control level [0.2+/-0.1 Hz (n=5)] after removal. The ORX-A/B-induced depolarization was well maintained in the presence of TTX (3x10(-7) M), CNQX (10(-6) M) and AP5 (10(-5) M). In voltage-clamp mode, removal of external Na+ suppressed both ORX-A/B-induced currents and shifted their reversal potentials from approximately -45 mV to -60 mV. In addition, ORX-A/B inhibited sustained K+ currents. These results suggest that ORX-A/B increase the firing frequency of LC neurons through the depolarization probably produced by both augmentation of the nonselective cationic conductance and inhibition of the sustained K+ conductance.
蓝斑（LC）包含去甲肾上腺素能神经元，这些神经元由食欲素（ORX）样免疫反应性轴突支配，并表达食欲素受体-1和-2。我们使用全细胞膜片钳技术研究了ORX-A和ORX-B（ORX-A/B）对分离的LC神经元的影响。在电流钳模式下，应用ORX-A（10^(-7) M）[53%的测试神经元；9.0±0.2 mV（n = 5）]或ORX-B（10^(-7) M）[38%的测试神经元；4.0±0.1 mV（n = 5）]可使LC神经元去极化。在应用过程中动作电位的发放频率增加[ORX-A中为1.1±0.2 Hz（n = 5）；ORX-B中为0.8±0.2 Hz（n = 5）]，去除后恢复到对照水平[0.2±0.1 Hz（n = 5）]。在存在TTX（3×10^(-7) M）、CNQX（10^(-6) M）和AP5（10^(-5) M）的情况下，ORX-A/B诱导的去极化得以很好维持。在电压钳模式下，去除细胞外Na+可抑制ORX-A/B诱导的电流，并使其反转电位从约-45 mV移至-60 mV。此外，ORX-A/B抑制持续性K+电流。这些结果表明，ORX-A/B可能通过增强非选择性阳离子电导和抑制持续性K+电导导致去极化，从而增加LC神经元的发放频率。
