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Integration of K+ and Cl- currents regulate steady-state and dynamic membrane potentials in cultured rat microglia.
J Physiol. 2005 Sep 15; 567(Pt 3):869-90.JP

Abstract

The role of ion channels and membrane potential (V(m)) in non-excitable cells has recently come under increased scrutiny. Microglia, the brain's resident immune cells, express voltage-gated Kv1.3 channels, a Kir2.1-like inward rectifier, a swelling-activated Cl(-) current and several other channels. We previously showed that Kv1.3 and Cl(-) currents are needed for microglial cell proliferation and that Kv1.3 is important for the respiratory burst. Although their mechanisms of action are unknown, one general role for these channels is to maintain a negative V(m). An impediment to measuring V(m) in non-excitable cells is that many have a very high electrical resistance, which makes them extremely susceptible to leak-induced depolarization. Using non-invasive V(m)-sensitive dyes, we show for the first time that the membrane resistance of microglial cells is several gigaohms; much higher than the seal resistance during patch-clamp recordings. Surprisingly, we observed that small current injections can evoke large V(m) oscillations in some microglial cells, and that injection of sinusoidal currents of varying frequency exposes a strong intrinsic electrical resonance in the 5- to 20-Hz frequency range in all microglial cells tested. Using a dynamic current clamp that we developed to actively compensate for the damage done by the patch-clamp electrode, we found that the V(m) oscillations and resonance were more prevalent and larger. Both types of electrical behaviour required Kv1.3 channels, as they were eliminated by the Kv1.3 blocker, agitoxin-2. To further determine how the ion currents integrate in these cells, voltage-clamp recordings from microglial cells displaying these behaviours were used to analyse the biophysical properties of the Kv1.3, Kir and Cl(-) currents. A mathematical model that incorporated only these three currents reproduced the observed V(m) oscillations and electrical resonance. Thus, the electrical behaviour of this 'non-excitable' cell type is much more complex than previously suspected, and might reflect a more common oversight in high resistance cells.

Authors+Show Affiliations

Division of Cellular and Molecular Biology, Toronto Western Research Institute, Ontario, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16020460

Citation

Newell, Evan W., and Lyanne C. Schlichter. "Integration of K+ and Cl- Currents Regulate Steady-state and Dynamic Membrane Potentials in Cultured Rat Microglia." The Journal of Physiology, vol. 567, no. Pt 3, 2005, pp. 869-90.
Newell EW, Schlichter LC. Integration of K+ and Cl- currents regulate steady-state and dynamic membrane potentials in cultured rat microglia. J Physiol. 2005;567(Pt 3):869-90.
Newell, E. W., & Schlichter, L. C. (2005). Integration of K+ and Cl- currents regulate steady-state and dynamic membrane potentials in cultured rat microglia. The Journal of Physiology, 567(Pt 3), 869-90.
Newell EW, Schlichter LC. Integration of K+ and Cl- Currents Regulate Steady-state and Dynamic Membrane Potentials in Cultured Rat Microglia. J Physiol. 2005 Sep 15;567(Pt 3):869-90. PubMed PMID: 16020460.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Integration of K+ and Cl- currents regulate steady-state and dynamic membrane potentials in cultured rat microglia. AU - Newell,Evan W, AU - Schlichter,Lyanne C, Y1 - 2005/07/14/ PY - 2005/7/16/pubmed PY - 2005/12/24/medline PY - 2005/7/16/entrez SP - 869 EP - 90 JF - The Journal of physiology JO - J Physiol VL - 567 IS - Pt 3 N2 - The role of ion channels and membrane potential (V(m)) in non-excitable cells has recently come under increased scrutiny. Microglia, the brain's resident immune cells, express voltage-gated Kv1.3 channels, a Kir2.1-like inward rectifier, a swelling-activated Cl(-) current and several other channels. We previously showed that Kv1.3 and Cl(-) currents are needed for microglial cell proliferation and that Kv1.3 is important for the respiratory burst. Although their mechanisms of action are unknown, one general role for these channels is to maintain a negative V(m). An impediment to measuring V(m) in non-excitable cells is that many have a very high electrical resistance, which makes them extremely susceptible to leak-induced depolarization. Using non-invasive V(m)-sensitive dyes, we show for the first time that the membrane resistance of microglial cells is several gigaohms; much higher than the seal resistance during patch-clamp recordings. Surprisingly, we observed that small current injections can evoke large V(m) oscillations in some microglial cells, and that injection of sinusoidal currents of varying frequency exposes a strong intrinsic electrical resonance in the 5- to 20-Hz frequency range in all microglial cells tested. Using a dynamic current clamp that we developed to actively compensate for the damage done by the patch-clamp electrode, we found that the V(m) oscillations and resonance were more prevalent and larger. Both types of electrical behaviour required Kv1.3 channels, as they were eliminated by the Kv1.3 blocker, agitoxin-2. To further determine how the ion currents integrate in these cells, voltage-clamp recordings from microglial cells displaying these behaviours were used to analyse the biophysical properties of the Kv1.3, Kir and Cl(-) currents. A mathematical model that incorporated only these three currents reproduced the observed V(m) oscillations and electrical resonance. Thus, the electrical behaviour of this 'non-excitable' cell type is much more complex than previously suspected, and might reflect a more common oversight in high resistance cells. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/16020460/Integration_of_K+_and_Cl__currents_regulate_steady_state_and_dynamic_membrane_potentials_in_cultured_rat_microglia_ L2 - https://doi.org/10.1113/jphysiol.2005.092056 DB - PRIME DP - Unbound Medicine ER -