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Spontaneously active and InsP 3 ‐activated ion channels in cell nuclei from rat cerebellar Purkinje and granule neurones
Author(s) -
Marchenko Sergey M.,
Yarotskyy Victor V.,
Kovalenko Tatia.,
Kostyuk Platon G.,
Thomas Roger C.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2004.081299
Subject(s) - cerebellum , nucleus , biophysics , microbiology and biotechnology , chemistry , ion channel , deep cerebellar nuclei , inhibitory postsynaptic potential , nucleoplasm , biology , receptor , cerebellar cortex , biochemistry , neuroscience , nucleolus
Increases in Ca 2+ 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 Ca 2+ 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 InsP 3 ‐ 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 InsP 3 receptors (InsP 3 Rs) were activated by InsP 3 with EC 50 = 0.67 μ m and a Hill coefficient of 2.5. Ca 2+ exhibited a biphasic effect on the receptors elevating its activity at low concentrations and inhibiting it at micromolar concentrations. InsP 3 in saturating concentrations did not prevent the inhibitory effect of Ca 2+ , but strongly increased InsP 3 R activity at resting Ca 2+ concentrations. These data are the first evidence for the presence of intranuclear sources of Ca 2+ in neurones. Ca 2+ release from the nuclear envelope may amplify Ca 2+ transients penetrating the nucleus from the cytoplasm or generate Ca 2+ transients in the nucleus independently of the cytoplasm.