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Developmental Regulation of Small-Conductance Ca²⁺-Activated K⁺ Channel Expression and Function in Rat Purkinje Neurons

Cingolani, LA; Gymnopoulos, M; Boccaccio, A; Stocker, M; Pedarzani, P; (2002) Developmental Regulation of Small-Conductance Ca²⁺-Activated K⁺ Channel Expression and Function in Rat Purkinje Neurons. Journal of Neuroscience , 22 (11) 4456 - 4467. 10.1523/JNEUROSCI.22-11-04456.2002. Green open access

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Abstract

Calcium transients play an important role in the early and later phases of differentiation and maturation of single neurons and neuronal networks. Small-conductance calcium-activated potassium channels of the SK type modulate membrane excitability and are important determinants of the firing properties of central neurons. Increases in the intracellular calcium concentration activate SK channels, leading to a hyperpolarization of the membrane potential, which in turn reduces the calcium inflow into the cell. This feedback mechanism is ideally suited to regulate the spatiotemporal occurrence of calcium transients. However, the role of SK channels in neuronal development has not been addressed so far. We have concentrated on the ontogenesis and function of SK channels in the developing rat cerebellum, focusing particularly on Purkinje neurons. Electrophysiological recordings combined with specific pharmacological tools have revealed for the first time the presence of an afterhyperpolarizing current (I_{AHP}) in immature Purkinje cells in rat cerebellar slices. The channel subunits underlying this current were identified as SK2 and localized by in situ hybridization and subunit-specific antibodies. Their expression level was shown to be high at birth and subsequently to decline during the first 3 weeks of postnatal life, both at the mRNA and protein levels. This developmental regulation was tightly correlated with the expression of I_{AHP} and the prominent role of SK2 channels in shaping the spontaneous firing pattern in young, but not in adult, Purkinje neurons. These results provide the first evidence of the developmental regulation and function of SK channels in central neurons.

Type: Article
Title: Developmental Regulation of Small-Conductance Ca²⁺-Activated K⁺ Channel Expression and Function in Rat Purkinje Neurons
Open access status: An open access version is available from UCL Discovery
DOI: 10.1523/JNEUROSCI.22-11-04456.2002
Publisher version: https://doi.org/10.1523/JNEUROSCI.22-11-04456.2002
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: SK channel, afterhyperpolarization, apamin, calcium-activated potassium current, development, Purkinje neurons
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/23123
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