Spontaneously active and InsP3-activated ion channels in cell nuclei from rat cerebellar Purkinje and granule neurones

Autor: S. M. Marchenko, R C Thomas, Tatiana N. Kovalenko, P. G. Kostyuk, Victor V. Yarotskyy
Rok vydání: 2005
Předmět:
Zdroj: The Journal of Physiology. 565:897-910
ISSN: 0022-3751
DOI: 10.1113/jphysiol.2004.081299
Popis: Increases in Ca2+ concentration in the nucleus of neurones modulate gene transcription and may be involved in activity-dependent long-term plasticity, apoptosis, and neurotoxicity. Little is currently known about the regulation of Ca2+ in the nuclei of neurones. Investigation of neuronal nuclei is hampered by the cellular heterogeneity of the brain where neurones comprise no more than 10% of the cells. The situation is further complicated by large differences in properties of different neurones. Here we report a method for isolating nuclei from identified central neurones. We employed this technique to study nuclei from rat cerebellar Purkinje and granule neurones. Patch-clamp recording from the nuclear membrane of Purkinje neurones revealed numerous large-conductance channels selective for monovalent cations. The nuclear membrane of Purkinje neurones also contained multiple InsP3- activated ion channels localized exclusively in the inner nuclear membrane with their receptor loci facing the nucleoplasm. In contrast, the nuclear membrane of granule neurones contained only a small number of mainly anion channels. Nuclear InsP3 receptors (InsP3Rs) were activated by InsP3 with EC50= 0.67 μm and a Hill coefficient of 2.5. Ca2+ exhibited a biphasic effect on the receptors elevating its activity at low concentrations and inhibiting it at micromolar concentrations. InsP3 in saturating concentrations did not prevent the inhibitory effect of Ca2+, but strongly increased InsP3R activity at resting Ca2+ concentrations. These data are the first evidence for the presence of intranuclear sources of Ca2+ in neurones. Ca2+ release from the nuclear envelope may amplify Ca2+ transients penetrating the nucleus from the cytoplasm or generate Ca2+ transients in the nucleus independently of the cytoplasm.
Databáze: OpenAIRE
Externí odkaz: