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Meth alters neuron and astrocyte activity; yet the underlying mechanism(s) is not fully understood. Here we assessed the impact of acute Meth on human fetal astrocytes (HFAs) using whole\u2010cell patch\u2010clamping. We found that HFAs displayed a large voltage\u2010gated K\n +<\/jats:sup>\n efflux (\n I<\/jats:italic>\n Kv<\/jats:sub>\n ) through K\n v<\/jats:sub>\n \/K\n v<\/jats:sub>\n \u2010like channels during membrane depolarization, and a smaller K\n +<\/jats:sup>\n influx (\n I<\/jats:italic>\n kir<\/jats:sub>\n )\n via<\/jats:italic>\n inward\u2010rectifying K\n ir<\/jats:sub>\n \/K\n ir<\/jats:sub>\n \u2010like channels during membrane hyperpolarization. Meth at a \u2018recreational\u2019 (20\u00a0\u03bcM) or toxic\/fatal (100\u00a0\u03bcM) concentration depolarized resting membrane potential (RMP) and suppressed\n I<\/jats:italic>\n Kv\/Kv\u2010like<\/jats:sub>\n . These changes were associated with a decreased time constant (\n \u01ac<\/jats:italic>\n ), and mimicked by blocking the two\u2010pore domain K\n +<\/jats:sup>\n (K\n 2P<\/jats:sub>\n )\/K\n 2P<\/jats:sub>\n \u2010like and K\n v<\/jats:sub>\n \/K\n v<\/jats:sub>\n \u2010like channels, respectively. Meth also diminished\n I<\/jats:italic>\n Kir\/Kir\u2010like<\/jats:sub>\n , but only at toxic\/fatal levels. Given that Meth is a potent agonist for the trace amine\u2010associated receptor type\u20101 (TAAR1), and TAAR1\u2010coupled cAMP\/cAMP\u2010activated protein kinase (PKA) cascade, we further evaluated whether the Meth impact on K\n +<\/jats:sup>\n efflux was mediated by this pathway. We found that antagonizing TAAR1 with\n N<\/jats:italic>\n \u2010(3\u2010Ethoxyphenyl)\u20104\u2010(1\u2010pyrrolidinyl)\u20103\u2010(trifluoromethyl)benzamide (EPPTB) reversed Meth\u2010induced suppression of\n I<\/jats:italic>\n Kv\/Kv\u2010like<\/jats:sub>\n ; and inhibiting PKA activity by H89 abolished Meth effects on suppressing\n I<\/jats:italic>\n Kv\/Kv\u2010like<\/jats:sub>\n . Antagonizing TAAR1 might also attenuate Meth\u2010induced RMP depolarization. Voltage\u2010gated Ca\n 2+<\/jats:sup>\n currents were not detected in HFAs. These novel findings demonstrate that Meth suppresses\n I<\/jats:italic>\n Kv\/Kv\u2010like<\/jats:sub>\n by facilitating the TAAR1\/G\n s<\/jats:sub>\n \/cAMP\/PKA cascade and altering the kinetics of K\n v<\/jats:sub>\n \/K\n v<\/jats:sub>\n \u2010like channel gating, but reduces K\n 2P<\/jats:sub>\n \/K\n 2P<\/jats:sub>\n \u2010like channel activity through other pathway(s), in HFAs. Given that Meth\u2010induced decrease in astrocytic K\n +<\/jats:sup>\n efflux through K\n 2P<\/jats:sub>\n \/K\n 2P<\/jats:sub>\n \u2010like and K\n v<\/jats:sub>\n \/K\n v<\/jats:sub>\n \u2010like channels reduces extracellular K\n +<\/jats:sup>\n levels, such reduction could consequently contribute to a decreased excitability of surrounding neurons.\n <\/jats:p>\n <\/jats:sec>\n \n Open science badges<\/jats:title>\n \n \n <\/jats:p>\n \n This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at\n https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>\n \n \n \n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jnc.14606","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T11:06:15Z","timestamp":1538996775000},"page":"29-45","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Methamphetamine decreases K\n +<\/sup>\n channel function in human fetal astrocytes by activating the trace amine\u2010associated receptor type\u20101"],"prefix":"10.1111","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7653-0388","authenticated-orcid":false,"given":"Sonya","family":"Dave","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogens and Immunity Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunjiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Seaton","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina E.","family":"Khodr","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Al\u2010Harthi","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiu\u2010Ti","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogens and Immunity Rush University Medical Center Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-012-9411-y"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-420118-7.00001-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.04.010"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2008.09.002"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906522106"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.60.6.1181"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(09)88005-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2016.48"},{"key":"e_1_2_7_10_1","unstructured":"ChenL. 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