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Microglia, the brain's resident immune cells, express voltage\u2010gated Kv1.3 channels, a Kir2.1\u2010like inward rectifier, a swelling\u2010activated Cl<jats:sup>\u2013<\/jats:sup>current and several other channels. We previously showed that Kv1.3 and Cl<jats:sup>\u2013<\/jats:sup>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<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>. An impediment to measuring<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>in non\u2010excitable cells is that many have a very high electrical resistance, which makes them extremely susceptible to leak\u2010induced depolarization. Using non\u2010invasive<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>\u2010sensitive 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\u2010clamp recordings. Surprisingly, we observed that small current injections can evoke large<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>oscillations in some microglial cells, and that injection of sinusoidal currents of varying frequency exposes a strong intrinsic electrical resonance in the 5\u2010 to 20\u2010Hz 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\u2010clamp electrode, we found that the<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>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\u20102. To further determine how the ion currents integrate in these cells, voltage\u2010clamp recordings from microglial cells displaying these behaviours were used to analyse the biophysical properties of the Kv1.3, Kir and Cl<jats:sup>\u2013<\/jats:sup>currents. A mathematical model that incorporated only these three currents reproduced the observed<jats:italic>V<\/jats:italic><jats:sub>m<\/jats:sub>oscillations and electrical resonance. Thus, the electrical behaviour of this \u2018non\u2010excitable\u2019 cell type is much more complex than previously suspected, and might reflect a more common oversight in high resistance cells.<\/jats:p>","DOI":"10.1113\/jphysiol.2005.092056","type":"journal-article","created":{"date-parts":[[2005,7,15]],"date-time":"2005-07-15T00:13:42Z","timestamp":1121386422000},"page":"869-890","source":"Crossref","is-referenced-by-count":58,"title":["Integration of K<sup>+<\/sup>and Cl<sup>\u2013<\/sup>currents regulate steady\u2010state and dynamic membrane potentials in cultured rat microglia"],"prefix":"10.1113","volume":"567","author":[{"given":"Evan W.","family":"Newell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyanne C.","family":"Schlichter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,9,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.2.H679"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01870526"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241497298"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02663.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)77383-2"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2003.08.001"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015548"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010958907271"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00083.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108211200"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.03.010"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00029-9"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00053-1"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.266.6.C1650"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1981.sp013634"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.95.4.617"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.275.2.C327"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00062-9"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00233542"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(97)00281-4"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-18-07127.1998"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011342200"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00398-O"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1251-05.2005"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2003.11.001"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-07-02460.1988"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1981.241.1.C9"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(08)60078-2"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021776"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79245-7"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.029249"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1996.76.2.683"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1994.71.2.583"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01547-2"},{"key":"e_1_2_5_36_1","first-page":"13","article-title":"Molecular mechanisms of microglial activation. 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