Glucose Deprivation Activates Diversity of Potassium Channels in Cultured Rat Hippocampal Neurons
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1. Glucose is one of the most important substrates for generating metabolic energy required for the maintenance of cellular functions. Glucose-mediated changes in neuronal firing pattern have been observed in the central nervous system of mammals. K+ channels directly regulated by intracellular ATP have been postulated as a linkage between cellular energetic metabolism and excitability; the functional roles ascribed to these channels include glucose-sensing to regulate energy homeostasis and neuroprotection under energy depletion conditions. The hippocampus is highly sensitive to metabolic insults and is the brain region most sensitive to ischemic damage. Because the identity of metabolically regulated potassium channels present in hippocampal neurons is obscure, we decided to study the biophysical properties of glucose-sensitive potassium channels in hippocampal neurons.
2. The dependence of membrane potential and the sensitivity of potassium channels to glucose and ATP in rat hippocampal neurons were studied in cell-attached and excised inside-out membrane patches.
3. We found that under hypoglycemic conditions, at least three types of potassium channels were activated; their unitary conductance values were 37, 147, and 241 pS in symmetrical K+, and they were sensitive to ATP. For K+ channels with unitary conductance of 37 and 241, when the membrane potential was depolarized the longer closed time constant diminished and this produced an increase in the open-state probability; nevertheless, the 147-pS channels were not voltage-dependent.
4. We propose that neuronal glucose-sensitive K+ channels in rat hippocampus include subtypes of ATP-sensitive channels with a potential role in neuroprotection during short-term or prolonged metabolic stress.
KEY WORDS:Glucose Potassium channels ATP Hippocampal neurons
The authors wish to express their gratitude to Adriana Hernández for technical assistance. This work has been partially supported by grant 229/03 from the “Fondo Ramón Álvarez-Buylla de Aldana,” Universidad de Colima, México to C. G. Onetti.
- Hall, A. C., Hoffmaster, R. M., Stern, E. L., Harrington, M. E., and Bickar, D. (1997). Suprachiasmatic nucleus neurons are glucose sensitive. J. Biol. Rhythms 12(5):338–400.Google Scholar
- Inagaki, N., Tsuura, Y., Namba, N., Masuda, K., Gonoi, T., Horie, M., Seino, Y., Mizuta, M., and Seino, S. (1995). Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J. Biol. Chem. 270:5691–5694.PubMedCrossRefGoogle Scholar
- Kakeim, M. and Noma, A. (1984). Adenosine-5´-triphosphate-sensitive single potassium channel in the atrioventricular node cell of the rabbit heart. J. Physiol. 352:265–284.Google Scholar
- Nakagawa, I., Ogawa, Y., Noriyama, Y., Nakase, H., Yamashita, M., and Sakaki, T. (2003). Chemical preconditioning prevents paradoxical increase in glutamate release during ischemia by activating ATP-dependent potassium channels in gerbil hippocampus. Exp. Neurol. 183:180–187.PubMedCrossRefGoogle Scholar