Mechanisms for L-channel-mediated increase in [Ca(2+)]i and its reduction by anti-bipolar drugs in cultured astrocytes combined with its mRNA expression in freshly isolated cells support the importance of astrocytic L-channels.

Abstract:

:The importance of Ca(2+) signaling in astrocytes is undisputed but a potential role of Ca(2+) influx via L-channels in the brain in vivo is disputed, although expression of these channels in cultured astrocytes is recognized. This study shows that an increase in free cytosolic Ca(2+) concentration ([Ca(2+)]i) in astrocytes in primary cultures in response to an increased extracellular K(+) concentration (45mM) is inhibited not only by nifedipine (confirming previous observations) but also to a very large extent by ryanodine, inhibiting ryanodine receptor-mediated release of Ca(2+), known to occur in response to an elevation in [Ca(2+)]i. This means that the actual influx of Ca(2+) is modest, which may contribute to the difficulty in demonstrating L-channel-mediated Ca(2+) currents in astrocytes in intact brain tissue. Chronic treatment with any of the 3 conventional anti-bipolar drugs lithium, carbamazepine or valproic acid similarly causes a pronounced inhibition of K(+)-mediated increase in [Ca(2+)]i. This is shown to be due to an inhibition of capacitative Ca(2+) influx, reflected by decreased mRNA and protein expression of the 'transient receptor potential channel' (TRPC1), a constituent of store-operated channels (SOCEs). Literature data are cited (i) showing that depolarization-mediated Ca(2+) influx in response to an elevated extracellular K(+) concentration is important for generation of Ca(2+) oscillations and for the stimulatory effect of elevated K(+) concentrations in intact, non-cultured brain tissue, and (ii) that Ca(2+) channel activity is dependent upon availability of metabolic substrates, including glycogen. Finally, expression of mRNA for Cav1.3 is demonstrated in freshly separated astrocytes from normal brain.

journal_name

Cell Calcium

journal_title

Cell calcium

authors

Yan E,Li B,Gu L,Hertz L,Peng L

doi

10.1016/j.ceca.2013.08.002

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

335-42

issue

5

eissn

0143-4160

issn

1532-1991

pii

S0143-4160(13)00117-6

journal_volume

54

pub_type

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