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Maturation of Rat Cerebellar Purkinje Cells Reveals an Atypical Ca2+ Channel Current That Is Inhibited by Omega-Agatoxin IVA and the Dihydropyridine (-)-(S)-Bay K8644

Maturation of Rat Cerebellar Purkinje Cells Reveals an Atypical Ca2+ Channel Current That Is Inhibited by Omega-Agatoxin IVA and the Dihydropyridine (-)-(S)-Bay K8644

Elizabeth W Tringham, C Elizabeth Payne, Jonathan R B Dupere, Maria M Usowicz

J Physiol. 2007 Feb 1;578(Pt 3):693-714.

PMID: 17124267

Abstract:

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 omega-agatoxin IVA at concentrations selective for P-type Ca2+ channels (approximately 85%; IC50, <1 nM) and by the dihydropyridine (-)-(S)-Bay K8644 (approximately 70%; IC50, approximately 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 omega-agatoxin IVA (approximately 86%; IC50, approximately 1 nM) and a minor component was inhibited by (R,S)-nimodipine (approximately 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 (approximately 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 omega-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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP98625264	(S)-(−)-Bay K8644		98625-26-4	Price

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