We are conducting molecular biological, physiological and cell biological investigations of the signal transduction mechanisms of neurotransmitter effects on brain neuron. For this purpose we have developed a unique method culturing neurons from specific brain nuclei such as cholinergic neurons from the basal forebrain and dopaminergic neurons from the substantia nigra; these nuclei are related to Alxheimer's and Parkinson's diseases.
Major emphasis is placed on the effects of slow acting neurotransmitters (substance P, neurotensin, somatostation, enkephalins, etc.) on inward rectifer K+ channels, Ca2+ channels and non-selective cation channels, particularly their signal transduction mechanisms (G proteins and messengers such as PKC). For example, we are investigating the interaction between these channels and G proteins by molecular biological methods (cloning of channels with the single cell mRNA method and mutation of channels and G proteins) and electrophysiological techniques (the patch clamp method, single channel recording and microinjection of anti-bodies and anti-sense oligonucleotides with Eppendorf microinjectors).
Publications:
1.Stanfield, P.R., Nakajima, Y. and Yamaguchi, K. (1985) Substance P raises neuronal membrane excitability by reducing inward rectification.Nature, 315: 498-501.
2.Takano, K., Stanfield, P.R., Nakajima, S. and Nakajima, Y. (1995) Protein kinase C-mediated inhibition of an inward rectifier potassium channel by substance P in nucleus basalis neurons.Neuron, 14: 999-1008.
3.Nakajima, Y., Nakajima, S., and Kozasa, T. (1996) Activation of G protein-coupled inward rectifier K+ channels in brain neurons requires association of G protein By-subunits with cell membrane.FEBS Letters, 390: 217-220.
4.Chien, P.-Y., Farkas, R.H., Nakajima, S. and Nakajima, Y. (1996) Single channel properties of the non-selective cation conductance induced by neurostensin in dopaminergic neurons.Proc. Natl. Acad. Sci. U.S.A.,93: 14917-14921.