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This Article Full Text Full Text (PDF) All Versions of this Article: 578/3/693    most recent jphysiol.2006.121905v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tringham, E. W. Articles by Usowicz, M. M. Search for Related Content PubMed PubMed Citation Articles by Tringham, E. W. Articles by Usowicz, M. M. Related Collections Neuroscience

¹ Department of Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK

To determine if the properties of Ca²⁺ channels in cerebellar Purkinje cells change during postnatal development, we recorded Ca²⁺ channel currents from Purkinje cells in cerebellar slices of mature (postnatal days (P) 40–50) and immature (P13–20) rats. We found that at P40–50, the somatic Ca²⁺ channel current was inhibited by -agatoxin IVA at concentrations selective for P-type Ca²⁺ channels (85%; IC₅₀, <1 nM) and by the dihydropyridine (–)-(S)-Bay K8644 (70%; IC₅₀, 40 nM). (–)-(S)-Bay K8644 is known to activate L-type Ca²⁺ channels, but the decrease in current was not secondary to the activation of L-type channels because inhibition by (–)-(S)-Bay K8644 persisted in the presence of the L-type channel blocker (R,S)-nimodipine. By contrast, at P13–20, the current was inhibited by -agatoxin IVA (86%; IC₅₀, 1 nM) and a minor component was inhibited by (R,S)-nimodipine (8%). The dihydropyridine (–)-(S)-Bay K8644 had no clear effect when applied alone, but in the presence of (R,S)-nimodipine it reduced the current (40%), suggesting that activation of L-type channels by (–)-(S)-Bay K8644 masks its inhibition of non-L-type channels. Our findings indicate that Purkinje neurons express a previously unrecognized type of Ca²⁺ channel that is inhibited by -agatoxin IVA, like prototypical P-type channels, and by (–)-(S)-Bay K8644, unlike classical P-type or L-type channels. During maturation, there is a decrease in the size of the L-type current and an increase in the size of the atypical Ca²⁺ channel current. These changes may contribute to the maturation of the electrical properties of Purkinje cells.

(Received 27 September 2006; accepted after revision 22 November 2006; first published online 23 November 2006)
Corresponding author M. Usowicz: Department of Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK. Email: m.m.usowicz{at}bris.ac.uk

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