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Query: UMLS:C0848283 (rundown)
 502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes swell during neuronal activity as they accumulate K+ to buffer the increase in external K+ released from neurons. This swelling activates volume-sensitive Cl- channels, which are thought to be important in regulatory volume decrease and in the response of the CNS to trauma and excitotoxicity. Mitogen-activated protein (MAP) kinases also are activated by cell volume changes, but their roles in volume regulation are unknown. We have investigated the role of tyrosine and MAP kinases in the activation of volume-activated Cl- channels in cultured astrocytes, using whole-cell patch-clamp recording and Western immunoblots. As previously described, hypo-osmotic solution induced an outwardly rectifying Cl- current, which was blocked by NPPB and SITS. This Cl- current did not depend on [Ca2+ ]i because it was still observed when 20 mM BAPTA was included in the pipette, but it did exhibit rundown when ATP was omitted. Inhibition of tyrosine kinases with genistein or tyrphostin A23 (but not the inactive agents daidzein and tyrphostin A1) blocked the Cl- current. The MAP kinase kinase (MEK) inhibitor PD 98059 reversibly inhibited activation of the Cl- current by hypo-osmotic solution. Western immunoblots showed that genistein or PD 98059 blocked activation of Erk-1 and Erk-2 by hypo-osmotic solution in astrocytes. Therefore, activation of tyrosine and MAP kinases by swelling is a critical step in the opening of volume-sensitive Cl- channels.
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PMID:Mitogen-activated protein and tyrosine kinases in the activation of astrocyte volume-activated chloride current. 945 30

A stretch-activated Cl- current (ICl) was investigated in cultured murine microglia using the whole-cell configuration of the patch-clamp technique. After application of membrane stretch, a Cl- current appeared within seconds, and its amplitude increased further within 3-8 min. ICl underwent rundown, which was prevented by addition of 4 mM ATP to the intracellular perfusing solution. The stretch-activated Cl- current exhibited outward rectification and did not show any voltage-dependent gating. Lowering the concentration of extracellular Cl- from 142 to 12 mM by equimolar substitution of Cl- with gluconate shifted the reversal potential of ICl by 41.6 +/- 1.8 mV in the depolarizing direction. 4, 4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) blocked ICl in a voltage- and time-dependent manner. At a test potential of +40 mV, a half-maximal blockade at 16.1 microM DIDS and at 71.0 microM SITS was determined for ICl. At a concentration of 200 microM, 5-nitro-2-(3-phenylpropylamino)benzoic acid or flufenamic acid blocked ICl by 88% and 75%, respectively. Each of these four Cl- channel blockers reversibly inhibited the ramification process of microglia, whereas blockers of voltage-gated Na+ and K+ channels did not affect the transformation of microglia from their ameboid into the ramified phenotype. It is suggested that in microglia functional stretch-activated Cl- channels are required for the induction of ramification but not for maintaining the ramified shape.
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PMID:Involvement of stretch-activated Cl- channels in ramification of murine microglia. 973 36