{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:31:07Z","timestamp":1790929867333,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,2,29]],"date-time":"2008-02-29T00:00:00Z","timestamp":1204243200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:p>In principal brain neurons, activation of Ca<jats:sup>2+<\/jats:sup>channels during an action potential, or spike, causes Ca<jats:sup>2+<\/jats:sup>entry into the cytosol within a millisecond. This in turn causes rapid activation of large conductance Ca<jats:sup>2+<\/jats:sup>\u2010gated channels, which enhances repolarization and abbreviates the spike. Here we describe another remarkable consequence of spike Ca<jats:sup>2+<\/jats:sup>entry: enhancement of the spike afterdepolarization. This action is also mediated by intracellular modulation of a particular class of K<jats:sup>+<\/jats:sup>channels, namely by inhibition of K<jats:sub>V<\/jats:sub>7 (KCNQ) channels. These channels generate the subthreshold, non\u2010inactivating M\u2010type K<jats:sup>+<\/jats:sup>current, whose activation curtails the spike afterdepolarization. Inhibition of K<jats:sub>V<\/jats:sub>7\/M by spike Ca<jats:sup>2+<\/jats:sup>entry allows the spike afterdepolarization to grow and can convert solitary spikes into high\u2010frequency bursts of action potentials. Through this novel intracellular modulatory action, Ca<jats:sup>2+<\/jats:sup>spike entry regulates the discharge mode and the signalling capacity of principal brain neurons.<\/jats:p>","DOI":"10.1113\/jphysiol.2007.148171","type":"journal-article","created":{"date-parts":[[2008,1,11]],"date-time":"2008-01-11T01:15:19Z","timestamp":1200014119000},"page":"1351-1363","source":"Crossref","is-referenced-by-count":36,"title":["Spike Ca<sup>2+<\/sup>influx upmodulates the spike afterdepolarization and bursting via intracellular inhibition of K<sub>V<\/sub>7\/M channels"],"prefix":"10.1113","volume":"586","author":[{"given":"Shmuel","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Yaari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,2,29]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15019.x"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1997.175bl.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021302"},{"key":"e_1_2_5_5_1","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1152\/jn.1993.70.4.1530","article-title":"Voltage dependence and activation kinetics of pharmacologically defined components of the high\u2010threshold calcium current in rat neocortical neurons","volume":"70","author":"Brown AM","year":"1993","journal-title":"J Neurophysiol"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01987-8"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.16.1.521"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1989.62.5.1149"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.084590"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1785"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7713"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016864"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(88)90373-2"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.95.6.1139"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90350-8"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-09-0849"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200208783"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00205.2006"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.2170\/jjphysiol.51.725"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.126367"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)90954-4"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00447-0"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1089-05.2005"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/43119"},{"key":"e_1_2_5_25_1","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/S0022-3565(24)36931-9","article-title":"Effects of the neuroprotective agent riluzole on the high voltage\u2010activated calcium channels of rat dorsal root ganglion neurons","volume":"282","author":"Huang CS","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/357244a0"},{"key":"e_1_2_5_27_1","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1152\/jn.1994.71.3.831","article-title":"Variant firing patterns in rat hippocampal pyramidal cells modulated by extracellular potassium","volume":"71","author":"Jensen MS","year":"1994","journal-title":"J Neurophysiol"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021301"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2560\/4\/2\/001"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-10-03312.2001"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/net.14.1.103.118"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(99)77134-1"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(96)10070-9"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.397ae.x"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1999.82.4.1895"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020862"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/27674"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(82)90320-1"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.12.4327"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-08-02612.1996"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2003.08.014"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0624-05.2005"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.127068"},{"key":"e_1_2_5_44_1","doi-asserted-by":"crossref","first-page":"6815","DOI":"10.1523\/JNEUROSCI.14-11-06815.1994","article-title":"N\u2010type Ca2+ channels are located on somata, dendrites, and a subpopulation of dendritic spines on live hippocampal pyramidal neurons","volume":"14","author":"Mills LR","year":"1994","journal-title":"J Neurosci"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90223-Z"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.14042"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.0571p.x"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(73)90290-2"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15-04-02995.1995"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.0205g.x"},{"key":"e_1_2_5_51_1","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0022-3565(24)37644-X","article-title":"Selectivity of linopirdine (DuP 996), a neurotransmitter release enhancer, in blocking voltage\u2010dependent and calcium\u2010activated potassium currents in hippocampal neurons","volume":"286","author":"Schnee ME","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(75)90817-3"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80032-X"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.071bz.x"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.028571"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0503966102"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0378-05.2005"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1987.sp016660"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7716524"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1997.6554"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(87)91631-3"},{"key":"e_1_2_5_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-12-04173.2001"},{"key":"e_1_2_5_63_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03645.2002"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-18-07118.1998"},{"key":"e_1_2_5_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.05.052"},{"key":"e_1_2_5_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5395.1890"},{"key":"e_1_2_5_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(06)81006-8"},{"key":"e_1_2_5_68_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1999.0720791.x"},{"key":"e_1_2_5_69_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.138131"},{"key":"e_1_2_5_70_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1152\/jn.1981.45.1.86","article-title":"Afterpotential generation in hippocampal pyramidal cells","volume":"45","author":"Wong RK","year":"1981","journal-title":"J Neurophysiol"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2002.tb00438.x"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.127670"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1621-05.2005"},{"key":"e_1_2_5_74_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0765-04.2004"},{"key":"e_1_2_5_75_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01333.2005"},{"key":"e_1_2_5_76_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204130200"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2007.148171","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2007.148171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T14:53:26Z","timestamp":1737816806000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2007.148171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,2,29]]},"references-count":75,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,3]]}},"alternative-id":["10.1113\/jphysiol.2007.148171"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2007.148171","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,2,29]]}}}