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Protein kinase C involvement in the resting and interferon-gamma-induced K+ channel profile of microglial cells.
J Neurosci Res. 1997 Feb 01; 47(3):233-41.JN

Abstract

The whole-cell configuration of the patch-clamp technique was used to study the involvement of protein kinase C (PKC) in the modulation of K+ channels in cultured microglia from newborn rats. We previously showed that 24-hr treatments with interferon-gamma (IFN-gamma) induce an increase of inward-rectifying (IR) and outward-rectifying (OR) current density and that the effect on OR was shared by bacterial lipopolysaccharide (LPS) (Visentin et al.: J Neurosci Res 42:439-451, 1995). In the present study, IFN-gamma (1-500 U/ml, 24 hr) enhanced IR current density up to threefold. The IFN-gamma effect was not detectable after shorter treatments (1-5 hr) and was abrogated by a protein synthesis inhibitor. The PKC activator phorbol myristate acetate (PMA) also increased IR current density, whereas the inactive alpha-4 isoform was ineffective. When IFN-gamma and PMA were co-applied, the effect was more than additive. Among the PKC inhibitors tested, staurosporine (STA)-but not calphostin C (CALP)-abolished the effect of IFN-gamma and of PMA and antagonized only partially that of co-applied IFN-gamma and PMA. OR currents were affected by treatment (24 hr) with PKC modulating agents in an opposite fashion. PMA depressed OR currents in control and in IFN-gamma (or LPS) treated cultures, even when added after pretreatment (with LPS) that was long enough to enhance OR channel expression. Both STA and CALP enhanced OR density in resting and IFN-gamma-stimulated cells but did not counteract the depressing effect of PMA. In conclusion, our data on IR suggest a relationship between the IFN-gamma effect on current density and PKC activation. However, we cannot conclude with certainty that IFN-gamma acts through PKC activation. Our data on OR support an inverse relationship between PKC activation and OR current density. Nevertheless, the lack of effect of PKC inhibitors on PMA-induced OR depression suggests that PMA may, in this case, act on a target different from PKC.

Authors+Show Affiliations

Laboratory of Pathophysiology, Istituto Superiore di Sanită, Rome, Italy.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9039645

Citation

Visentin, S, and G Levi. "Protein Kinase C Involvement in the Resting and Interferon-gamma-induced K+ Channel Profile of Microglial Cells." Journal of Neuroscience Research, vol. 47, no. 3, 1997, pp. 233-41.
Visentin S, Levi G. Protein kinase C involvement in the resting and interferon-gamma-induced K+ channel profile of microglial cells. J Neurosci Res. 1997;47(3):233-41.
Visentin, S., & Levi, G. (1997). Protein kinase C involvement in the resting and interferon-gamma-induced K+ channel profile of microglial cells. Journal of Neuroscience Research, 47(3), 233-41.
Visentin S, Levi G. Protein Kinase C Involvement in the Resting and Interferon-gamma-induced K+ Channel Profile of Microglial Cells. J Neurosci Res. 1997 Feb 1;47(3):233-41. PubMed PMID: 9039645.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein kinase C involvement in the resting and interferon-gamma-induced K+ channel profile of microglial cells. AU - Visentin,S, AU - Levi,G, PY - 1997/2/1/pubmed PY - 2000/6/20/medline PY - 1997/2/1/entrez SP - 233 EP - 41 JF - Journal of neuroscience research JO - J Neurosci Res VL - 47 IS - 3 N2 - The whole-cell configuration of the patch-clamp technique was used to study the involvement of protein kinase C (PKC) in the modulation of K+ channels in cultured microglia from newborn rats. We previously showed that 24-hr treatments with interferon-gamma (IFN-gamma) induce an increase of inward-rectifying (IR) and outward-rectifying (OR) current density and that the effect on OR was shared by bacterial lipopolysaccharide (LPS) (Visentin et al.: J Neurosci Res 42:439-451, 1995). In the present study, IFN-gamma (1-500 U/ml, 24 hr) enhanced IR current density up to threefold. The IFN-gamma effect was not detectable after shorter treatments (1-5 hr) and was abrogated by a protein synthesis inhibitor. The PKC activator phorbol myristate acetate (PMA) also increased IR current density, whereas the inactive alpha-4 isoform was ineffective. When IFN-gamma and PMA were co-applied, the effect was more than additive. Among the PKC inhibitors tested, staurosporine (STA)-but not calphostin C (CALP)-abolished the effect of IFN-gamma and of PMA and antagonized only partially that of co-applied IFN-gamma and PMA. OR currents were affected by treatment (24 hr) with PKC modulating agents in an opposite fashion. PMA depressed OR currents in control and in IFN-gamma (or LPS) treated cultures, even when added after pretreatment (with LPS) that was long enough to enhance OR channel expression. Both STA and CALP enhanced OR density in resting and IFN-gamma-stimulated cells but did not counteract the depressing effect of PMA. In conclusion, our data on IR suggest a relationship between the IFN-gamma effect on current density and PKC activation. However, we cannot conclude with certainty that IFN-gamma acts through PKC activation. Our data on OR support an inverse relationship between PKC activation and OR current density. Nevertheless, the lack of effect of PKC inhibitors on PMA-induced OR depression suggests that PMA may, in this case, act on a target different from PKC. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/9039645/Protein_kinase_C_involvement_in_the_resting_and_interferon_gamma_induced_K+_channel_profile_of_microglial_cells_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0360-4012&date=1997&volume=47&issue=3&spage=233 DB - PRIME DP - Unbound Medicine ER -