Effects of barbiturates on ATP-sensitive K channels in rat substantia nigra
被引:8
作者:
Ohtsuka, T
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Ohtsuka, T
[1
]
Ishiwa, D
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Ishiwa, D
[1
]
Kamiya, Y
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Kamiya, Y
[1
]
Itoh, H
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Itoh, H
[1
]
Nagata, I
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Nagata, I
[1
]
Saito, Y
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Saito, Y
[1
]
Yamada, Y
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Yamada, Y
[1
]
Sumitomo, M
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Sumitomo, M
[1
]
Andoh, T
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Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, JapanYokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
Andoh, T
[1
]
机构:
[1] Yokohama City Univ, Dept Anesthesiol & Crit Care Med, Grad Sch Med, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
thiopental;
pentobarbital;
K channel;
neuroprotection;
D O I:
10.1016/j.neuroscience.2005.08.078
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
ATP-sensitive K channels are widely expressed in cytoplasmic membranes of neurons, and they couple cell metabolism to excitability. They are thought to be involved in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity by hyperpolarizing neurons and reducing excitability. Although barbiturates are often used in patients with brain ischemia, the effects of these agents on neuronal ATP-sensitive K channels have not been clarified. We studied the effects of thiopental and pentobarbital on surface ATP-sensitive K channels in principal neurons of rat substantia nigra pars compacta. Whole cell voltage- and current-clamp recordings were made using rat midbrain slices. ATP-sensitive K channels were activated by intracellular dialysis with an ATP-free pipette solution during perfusion with a glucose-free solution. When the pipette solution contained 4 mM ATP and the perfusing solution contained 25 mM glucose, the membrane current at -60 mV remained stable. When intracellular ATP was depleted, hyperpolarization and an outward current developed slowly. Although thiopental did not affect the membrane current in the presence of ATP and glucose, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion at 100 and 300 mu M. Thiopental reduced the ATP depletion-induced outward current by 4.7%, 36.7% and 87% at 30, 100 and 300 mu M, respectively. The high dose of pentobarbital also exhibited similar effects on ATP-sensitive K channels. These results suggest that barbiturates at high concentrations but not at clinically relevant concentrations inhibit ATP-sensitive K channels activated by intracellular ATP depletion in rat substantia nigra. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.