{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:55:01Z","timestamp":1778748901902,"version":"3.51.4"},"reference-count":19,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2014,3,1]],"date-time":"2014-03-01T00:00:00Z","timestamp":1393632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["ASSAY and Drug Development Technologies"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:p>\n                    Voltage-gated Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels play essential roles in control of neurosecretion and muscle contraction. The pharmacological significance of Ca\n                    <jats:sub>v<\/jats:sub>\n                    channels stem from their identification as the molecular targets of calcium blockers used in the treatment of cardiovascular diseases, such as hypertension, angina, and arrhythmia, and neurologic diseases, such as pain and seizure. It has been proposed that state-dependent Ca\n                    <jats:sub>v<\/jats:sub>\n                    inhibitors, that is, those that preferentially bind to channels in open or inactivated states, may improve the therapeutic window over relatively state-independent Ca\n                    <jats:sub>v<\/jats:sub>\n                    inhibitors. High-throughput fluorescent-based functional assays have been useful in screening chemical libraries to identify Ca\n                    <jats:sub>v<\/jats:sub>\n                    inhibitors. However, hit confirmation, mechanism of action, and subtype selectivity are better suited to automated patch clamp assays that have sufficient capacity to handle the volume of compounds identified during screening, even of modest sized libraries (\u2264500,000 compounds), and the flexible voltage control that allows evaluation of state-dependent drug blocks. IonWorks\u2122 Barracuda (IWB), the newest generation of IonWorks instruments, provides the opportunity to accelerate the Ca\n                    <jats:sub>v<\/jats:sub>\n                    drug discovery studies in an automated patch clamp platform in 384-well format capable of medium throughput screening and profiling studies. We have validated hCa\n                    <jats:sub>v<\/jats:sub>\n                    1.2, hCa\n                    <jats:sub>v<\/jats:sub>\n                    2.1, hCa\n                    <jats:sub>v<\/jats:sub>\n                    2.2, and hCa\n                    <jats:sub>v<\/jats:sub>\n                    3.2 channels assays on the IWB platform (population patch clamp mode) and demonstrated that the biophysical characteristics of the channels (activation, inactivation, and steady-state inactivation) obtained with the IWB system are consistent with known subtype-specific characteristics. Using standard reference compounds (nifedipine, BAY K8644, verapamil, mibefradil, and pimozide), we demonstrated subtype-selective and state- and use-dependent characteristics of drug\u2013channel interactions. Here we describe the design and validation of novel robust high-throughput Ca\n                    <jats:sub>v<\/jats:sub>\n                    channel assays on the IWB platform. The assays can be used to screen focused compound libraries for state-dependent Ca\n                    <jats:sub>v<\/jats:sub>\n                    channel antagonists, to prioritize compounds for potency or to counterscreen for Ca\n                    <jats:sub>v<\/jats:sub>\n                    subtype selectivity.\n                  <\/jats:p>","DOI":"10.1089\/adt.2013.552","type":"journal-article","created":{"date-parts":[[2014,2,28]],"date-time":"2014-02-28T12:01:52Z","timestamp":1393588912000},"page":"110-119","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":41,"title":["Evaluating State Dependence and Subtype Selectivity of Calcium Channel Modulators in Automated Electrophysiology Assays"],"prefix":"10.1177","volume":"12","author":[{"given":"Yuri A.","family":"Kuryshev","sequence":"first","affiliation":[{"name":"ChanTest Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur M.","family":"Brown","sequence":"additional","affiliation":[{"name":"ChanTest Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emir","family":"Duzic","sequence":"additional","affiliation":[{"name":"ChanTest Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn E.","family":"Kirsch","sequence":"additional","affiliation":[{"name":"ChanTest Corporation"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,3,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.4.5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/154065803770381075"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1602\/neurorx.2.4.662"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568007043336743"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.60.5.1121"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703604"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2008.171"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:JOBB.0000008022.50702.1a"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.55.3.336"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/108705719900400206"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.24.040184.002131"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)24034-4"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)38902-5"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2011.437"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-02-00396.2002"},{"issue":"1","key":"e_1_3_3_17_2","first-page":"1","article-title":"Voltage-dependent calcium channels","volume":"24","author":"Lacinov\u00e1 L","year":"2005","unstructured":"Lacinov\u00e1 L: Voltage-dependent calcium channels. Gen Physiol Biophys, 2005; 24 Suppl 1:1\u201378.","journal-title":"Gen Physiol Biophys"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057112456599"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2010.0333"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2009.02.002"}],"container-title":["ASSAY and Drug Development Technologies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/adt.2013.552","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/adt.2013.552","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/adt.2013.552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:20:10Z","timestamp":1777393210000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/adt.2013.552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1089\/adt.2013.552"],"URL":"https:\/\/doi.org\/10.1089\/adt.2013.552","relation":{},"ISSN":["1540-658X","1557-8127"],"issn-type":[{"value":"1540-658X","type":"print"},{"value":"1557-8127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3]]}}}