Activation of ryanodine receptors induces calcium influx in a neuroblastoma cell line lacking calcium influx factor activity

Document Type

Article

Publication Title

Biochemical Journal

ISSN

0264-6021

Volume

386

Issue

2

DOI

10.1042/BJ20040900

First Page

291

Last Page

296

Publication Date

3-1-2005

Abstract

We have further characterized the Ca signalling properties of the NG115-401L (or 401L) neuroblastoma cell line, which has served as an important cell line for investigating SOC (store-operated channel) influx pathways. These cells possess an unusual Ca signalling phenotype characterized by the absence of Ca influx when Ca stores are depleted by inhibitors of SERCA (sarcoplasmic/endoplasmic reticulum Ca -ATPase). Previous studies found that Ca -store depletion does not produce a CIF (Ca influx factor) activity in 401L cells. These observations have prompted the question whether 401L cells possess the signalling machinery that permits non-voltage-gated Ca influx to occur. We tested the hypothesis that ryanodine-sensitive Ca pools and activation of RyRs (ryanodine receptors) constitute a signalling pathway capable of inducing Ca influx in 401L cells. We found that 401L cells express mRNA for RyR1 and RyR2 and that RyR activators induced Ca release. Activation of RyRs robustly couples with Ca influx responses in 401L cells, in sharp contrast with absence of Ca influx when cells are treated with SERCA inhibitors. Thus it is clear that 401L cells, despite lacking depletion-induced Ca influx pathways, express the functional components of a Ca influx pathway under the control of RyR function. These findings further support the importance of the 401L cell line as an important cell phenotype for deciphering Ca influx regulation. © 2005 Biochemical Society. 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+

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