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Ion channels in rat microglia and their different sensitivity to lipopolysaccharide and interferon-gamma.
J Neurosci Res. 1995 Nov 01; 42(4):439-51.JN

Abstract

In order to study the voltage-dependent ion channels in microglia, and their possible modulation by pro-inflammatory substances like lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) we employed the patch-clamp technique on purified rat microglial cell subcultures grown for 1 - 5 days in control condition or after a 24 hour treatment with those agents. Regardless of the culture condition, almost 100% of the cells presented inward-rectifying (IR) K+ currents identified by the following features: (a) extracellular K(+)-dependence of Vrev and whole-cell conductance; (b) inward-rectifying property; (c) channel blocking mechanism by Cs+; and (d) single channel conductance of 27 pS. A 'n' type outward-rectifying (OR) K+ current was present in 30% of the cells during the first 2 days of subcultivation. Its occurrence was strongly dependent on the preparation, varying from 0% to almost 80%, and it decreased to 13% of the cells after three days in culture. It showed the following features: (i) threshold of activation close to -30 mV; (ii) sigmoid current onset; (iii) voltage-dependent kinetics; and (iv) sensitivity to 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Furthermore, we detected two ion currents not previously described in microglia: (i) a slowly activating outward current which appeared at potentials more positive than +20 mV and with a reversal potential close to 0 mV, tentatively identified as a proton current; and (ii) a Cl- conductance identified in ion substitution experiments as the current sensitive to the Cl- channel blocker SITS. The two agents, LPS (20 - 2,000 ng/ml) and IFN-gamma (10 - 100 u/ml), shared the following effects: (a) enhancement of membrane capacitance, and (b) increase of OR current amplitude and frequency of occurrence. Moreover, IFN-gamma was also able to increase IR current density, especially in cells with ameboid morphology, while LPS was ineffective. We conclude that the voltage-dependent ion channel pattern of microglia is more complex than previously thought and that activating agents such as LPS and IFN-gamma share some electrophysiological effects, but differ in others.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

8568930

Citation

Visentin, S, et al. "Ion Channels in Rat Microglia and Their Different Sensitivity to Lipopolysaccharide and Interferon-gamma." Journal of Neuroscience Research, vol. 42, no. 4, 1995, pp. 439-51.
Visentin S, Agresti C, Patrizio M, et al. Ion channels in rat microglia and their different sensitivity to lipopolysaccharide and interferon-gamma. J Neurosci Res. 1995;42(4):439-51.
Visentin, S., Agresti, C., Patrizio, M., & Levi, G. (1995). Ion channels in rat microglia and their different sensitivity to lipopolysaccharide and interferon-gamma. Journal of Neuroscience Research, 42(4), 439-51.
Visentin S, et al. Ion Channels in Rat Microglia and Their Different Sensitivity to Lipopolysaccharide and Interferon-gamma. J Neurosci Res. 1995 Nov 1;42(4):439-51. PubMed PMID: 8568930.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ion channels in rat microglia and their different sensitivity to lipopolysaccharide and interferon-gamma. AU - Visentin,S, AU - Agresti,C, AU - Patrizio,M, AU - Levi,G, PY - 1995/11/1/pubmed PY - 1995/11/1/medline PY - 1995/11/1/entrez SP - 439 EP - 51 JF - Journal of neuroscience research JO - J Neurosci Res VL - 42 IS - 4 N2 - In order to study the voltage-dependent ion channels in microglia, and their possible modulation by pro-inflammatory substances like lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) we employed the patch-clamp technique on purified rat microglial cell subcultures grown for 1 - 5 days in control condition or after a 24 hour treatment with those agents. Regardless of the culture condition, almost 100% of the cells presented inward-rectifying (IR) K+ currents identified by the following features: (a) extracellular K(+)-dependence of Vrev and whole-cell conductance; (b) inward-rectifying property; (c) channel blocking mechanism by Cs+; and (d) single channel conductance of 27 pS. A 'n' type outward-rectifying (OR) K+ current was present in 30% of the cells during the first 2 days of subcultivation. Its occurrence was strongly dependent on the preparation, varying from 0% to almost 80%, and it decreased to 13% of the cells after three days in culture. It showed the following features: (i) threshold of activation close to -30 mV; (ii) sigmoid current onset; (iii) voltage-dependent kinetics; and (iv) sensitivity to 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Furthermore, we detected two ion currents not previously described in microglia: (i) a slowly activating outward current which appeared at potentials more positive than +20 mV and with a reversal potential close to 0 mV, tentatively identified as a proton current; and (ii) a Cl- conductance identified in ion substitution experiments as the current sensitive to the Cl- channel blocker SITS. The two agents, LPS (20 - 2,000 ng/ml) and IFN-gamma (10 - 100 u/ml), shared the following effects: (a) enhancement of membrane capacitance, and (b) increase of OR current amplitude and frequency of occurrence. Moreover, IFN-gamma was also able to increase IR current density, especially in cells with ameboid morphology, while LPS was ineffective. We conclude that the voltage-dependent ion channel pattern of microglia is more complex than previously thought and that activating agents such as LPS and IFN-gamma share some electrophysiological effects, but differ in others. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/8568930/Ion_channels_in_rat_microglia_and_their_different_sensitivity_to_lipopolysaccharide_and_interferon_gamma_ L2 - https://doi.org/10.1002/jnr.490420402 DB - PRIME DP - Unbound Medicine ER -