{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:01:54Z","timestamp":1787025714769,"version":"build-2736575974"},"reference-count":39,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:sec>\n                    <jats:title>Object<\/jats:title>\n                    <jats:p>\n                      The L-type Ca\n                      <jats:sup>++<\/jats:sup>\n                      channel antagonists like nimodipine have limited efficacy against vasospasm after subarachnoid hemorrhage (SAH). The authors tested the hypothesis that this is because SAH alters these channels, rendering them less responsible for contraction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Basilar artery smooth muscle cells were isolated 4, 7, and 21 days after SAH in dogs, and Ca\n                      <jats:sup>++<\/jats:sup>\n                      channel currents were recorded in 10-mmol\/L barium. Proteins for \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      subunits of L-type Ca\n                      <jats:sup>++<\/jats:sup>\n                      channels were measured by immunoblotting and isometric tension recordings done on rings of the basilar artery.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      High voltage\u2013activated (HVA) Ca\n                      <jats:sup>++<\/jats:sup>\n                      channel currents were significantly decreased and low voltage\u2013activated (LVA) currents increased during vasospasm 4, 7, and 21 days after SAH (p &lt; 0.05). Vasospasm was associated with a significant decrease in the number of cells with negligible LVA current while the number of cells in which the LVA current formed greater than 50% of the maximal current increased (p &lt; 0.01). Window currents through LVA and HVA channels were significantly reduced. All changes correlated with the severity of vasospasm. There was an increase in protein for Ca\n                      <jats:sub>v<\/jats:sub>\n                      3.1 and Ca\n                      <jats:sub>v<\/jats:sub>\n                      3.3 \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      subunits that comprise T-type Ca\n                      <jats:sup>++<\/jats:sup>\n                      channels, a decrease in L-type (Ca\n                      <jats:sub>v<\/jats:sub>\n                      1.2 and Ca\n                      <jats:sub>v<\/jats:sub>\n                      1.3) and an increase in R-type (Ca\n                      <jats:sub>v<\/jats:sub>\n                      2.3) Ca\n                      <jats:sup>++<\/jats:sup>\n                      channel \u03b1\n                      <jats:sub>1<\/jats:sub>\n                      subunits. Functionally, however, isometric tension studies showed vasospastic arteries still relaxed with nimodipine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Voltage-dependent Ca\n                      <jats:sup>++<\/jats:sup>\n                      channels are altered in cerebral arteries after SAH. While decreased L-type channels may account for the lack of efficacy of nimodipine clinically, there may be other reasons such as inadequate dose, effect of nimodipine on other cellular targets, and mechanisms of vasospasm other than smooth muscle contraction mediated by activation of L-type Ca\n                      <jats:sup>++<\/jats:sup>\n                      channels.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3171\/2010.2.jns091038","type":"journal-article","created":{"date-parts":[[2010,3,12]],"date-time":"2010-03-12T08:47:48Z","timestamp":1268383668000},"page":"870-880","source":"Crossref","is-referenced-by-count":24,"title":["Alteration in voltage-dependent calcium channels in dog basilar artery after subarachnoid hemorrhage"],"prefix":"10.3171","volume":"113","author":[{"given":"Elena","family":"Nikitina","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Chicago Medical Center and Pritzker School of Medicine, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Keenan Research Centre and the Li Ka Shing Knowledge Institute of St. Michael's Hospital and Department of Surgery, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago Medical Center and Pritzker School of Medicine, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Du","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Chicago Medical Center and Pritzker School of Medicine, Chicago, Illinois; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyuan","family":"Shang","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Keenan Research Centre and the Li Ka Shing Knowledge Institute of St. Michael's Hospital and Department of Surgery, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinglu","family":"Ai","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Keenan Research Centre and the Li Ka Shing Knowledge Institute of St. Michael's Hospital and Department of Surgery, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Loch","family":"Macdonald","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Keenan Research Centre and the Li Ka Shing Knowledge Institute of St. Michael's Hospital and Department of Surgery, University of Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns091038","series-title":"J Cereb Blood Flow Metab","first-page":"75","article-title":"Molecular profile of vascular ion channels after experimental subarachnoid hemorrhage","volume":"24","author":"Aihara","year":"2004"},{"key":"b2-jns091038","series-title":"Pharmacol Ther","first-page":"1","article-title":"Calcium channels in cerebral arteries","volume":"68","author":"Alborch","year":"1995"},{"key":"b3-jns091038","series-title":"N Engl J Med","first-page":"619","article-title":"Cerebral arterial spasm\u2014a controlled trial of nimodipine in patients with subarachnoid hemorrhage","volume":"308","author":"Allen","year":"1983"},{"key":"b4-jns091038","series-title":"Pharmacol Res","first-page":"120","article-title":"Nimodipine can improve cerebral metabolism and outcome in patients with severe head trauma","volume":"59","author":"Aslan","year":"2009"},{"key":"b5-jns091038","series-title":"Chin J Traumatol","first-page":"224","article-title":"Changes of neuronal calcium channel following brain damage induced by injection of pertussis bacilli in rats","volume":"5","author":"Chen","year":"2002"},{"key":"b6-jns091038","series-title":"J Neurophysiol","first-page":"1","article-title":"Glucocorticoid receptor activation lowers the threshold for NMDA-receptor-dependent homosynaptic long-term depression in the hippocampus through activation of voltage-dependent calcium channels","volume":"78","author":"Coussens","year":"1997"},{"key":"b7-jns091038","series-title":"J Clin Neurosci","first-page":"151","article-title":"A review of cerebral vasospasm in aneurysmal subarachnoid haemorrhage Part III: mechanisms of action of calcium antagonists","volume":"1","author":"Dorsch","year":"1994"},{"issue":"2","key":"b8-jns091038","series-title":"Cochrane Database Syst Rev","first-page":"CD000277","article-title":"Calcium antagonists for aneurysmal subarachnoid haemorrhage","author":"Feigin","year":"2000"},{"key":"b9-jns091038","series-title":"J Neurosurg","first-page":"548","article-title":"A randomized trial of nicardipine in subarachnoid hemorrhage: angiographic and transcranial Doppler ultrasound results. A report of the Cooperative Aneurysm Study","volume":"78","author":"Haley","year":"1993"},{"key":"b10-jns091038","series-title":"Clin Neurol Neurosurg","first-page":"784","article-title":"Feasibility and safety of intrathecal nimodipine on posthaemorrhagic cerebral vasospasm refractory to medical and endovascular therapy","volume":"110","author":"H\u00e4nggi","year":"2008"},{"key":"b11-jns091038","series-title":"J Clin Invest","first-page":"875","article-title":"Possible cellular mechanism for cerebral vasospasm after experimental subarachnoid hemorrhage in the dog","volume":"80","author":"Harder","year":"1987"},{"key":"b12-jns091038","series-title":"J Neurosurg","first-page":"503","article-title":"Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys","volume":"83","author":"Hino","year":"1995"},{"key":"b13-jns091038","series-title":"Circ Res","first-page":"419","article-title":"Emergence of a R-type Ca2+ channel (CaV 2.3) contributes to cerebral artery constriction after subarachnoid hemorrhage","volume":"96","author":"Ishiguro","year":"2005"},{"key":"b14-jns091038","series-title":"J Cereb Blood Flow Metab","first-page":"797","article-title":"Voltage-gated K+ channel dysfunction in myocytes from a dog model of subarachnoid hemorrhage","volume":"28","author":"Jahromi","year":"2008"},{"key":"b15-jns091038","series-title":"J Physiol","first-page":"535","article-title":"Calcium currents elicited by voltage steps and steady voltages in myocytes isolated from the rat basilar artery","volume":"469","author":"Langton","year":"1993"},{"key":"b16-jns091038","series-title":"Eur J Pharmacol","first-page":"199","article-title":"The nicotinic acetylcholine receptor of the bovine chromaffin cell, a new target for dihydropyridines","volume":"247","author":"L\u00f3pez","year":"1993"},{"key":"b17-jns091038","series-title":"Stroke","first-page":"3015","article-title":"Clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage (CONSCIOUS-1): randomized, double-blind, placebo-controlled phase 2 dose-finding trial","volume":"39","author":"Macdonald","year":"2008"},{"key":"b18-jns091038","series-title":"Cerebral Vasospasm","year":"2001"},{"key":"b19-jns091038","series-title":"Blood Vessels","first-page":"498","article-title":"Morphometric analysis of monkey cerebral arteries exposed in vivo to whole blood, oxyhemoglobin, methemoglobin, and bilirubin","volume":"28","author":"Macdonald","year":"1991"},{"key":"b20-jns091038","series-title":"Neurosurgery","first-page":"962","article-title":"Papaverine-sensitive vasospasm and arterial contractility and compliance after subarachnoid hemorrhage in dogs","volume":"37","author":"Macdonald","year":"1995"},{"key":"b21-jns091038","series-title":"Am J Physiol Heart Circ Physiol","first-page":"H2329","article-title":"Calcium sensitivity of vasospastic basilar artery after experimental subarachnoid hemorrhage","volume":"290","author":"Macdonald","year":"2006"},{"key":"b22-jns091038","series-title":"J Physiol","first-page":"259","article-title":"Evidence for multiple types of Ca2+ channels in acutely isolated hippocampal CA3 neurones of the guinea-pig","volume":"433","author":"Mogul","year":"1991"},{"key":"b23-jns091038","series-title":"J Physiol","first-page":"523","article-title":"Voltage-dependent calcium channels of dog basilar artery","volume":"580","author":"Nikitina","year":"2007"},{"key":"b24-jns091038","series-title":"Cell","first-page":"89","article-title":"Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels","volume":"102","author":"Platzer","year":"2000"},{"key":"b25-jns091038","series-title":"Cardiovasc Res","first-page":"177","article-title":"Transient down-regulation of L-type Ca(2+) channel and dystrophin expression after balloon injury in rat aortic cells","volume":"49","author":"Quignard","year":"2001"},{"key":"b26-jns091038","series-title":"Zentralbl Neurochir","first-page":"79","article-title":"[Recommendations for the management of patients with aneurysmal subarachnoid hemorrhage.]","volume":"66","author":"Raabe","year":"2005"},{"key":"b27-jns091038","series-title":"J Physiol","first-page":"411","article-title":"Mechanisms of GABA and glycine depolarization-induced calcium transients in rat dorsal horn neurons","volume":"476","author":"Reichling","year":"1994"},{"key":"b28-jns091038","series-title":"J Neurochem","first-page":"2224","article-title":"Pharmacological evidence for the involvement of calcium\/calmodulin in serotonin 5-HT3 receptor-mediated cation permeability in NG 108\u201315 cells","volume":"62","author":"Riad","year":"1994"},{"key":"b29-jns091038","series-title":"Biochim Biophys Acta","first-page":"95","article-title":"Differential expression of voltage-gated Ca(2+)-currents in cultivated aortic myocytes","volume":"1160","author":"Richard","year":"1992"},{"key":"b30-jns091038","series-title":"Neurocrit Care","first-page":"93","article-title":"Inhibition of cerebral vasoconstriction by dantrolene and nimodipine","volume":"10","author":"Salomone","year":"2009"},{"key":"b31-jns091038","series-title":"Circ Res","first-page":"1330","article-title":"Increase in functional Ca2+ channels in cerebral smooth muscle with renal hypertension","volume":"82","author":"Simard","year":"1998"},{"key":"b32-jns091038","series-title":"J Physiol","first-page":"455","article-title":"Ca2+ currents in single myocytes from human mesenteric arteries: evidence for a physiological role of L-type channels","volume":"457","author":"Smirnov","year":"1992"},{"key":"b33-jns091038","series-title":"J Physiol","first-page":"139","article-title":"A model of the L-type Ca2+ channel in rat ventricular myocytes: ion selectivity and inactivation mechanisms","volume":"529","author":"Sun","year":"2000"},{"key":"b34-jns091038","series-title":"J Cereb Blood Flow Metab","first-page":"1761","article-title":"Microthrombosis after aneurysmal subarachnoid hemorrhage: an additional explanation for delayed cerebral ischemia","volume":"28","author":"Vergouwen","year":"2008"},{"key":"b35-jns091038","series-title":"J Cereb Blood Flow Metab","first-page":"1293","article-title":"Dihydropyridine calcium antagonists increase fibrinolytic activity: a systematic review","volume":"27","author":"Vergouwen","year":"2007"},{"key":"b36-jns091038","series-title":"J Neurosurg","first-page":"173","article-title":"Time course of vasospasm in man","volume":"48","author":"Weir","year":"1978"},{"key":"b37-jns091038","series-title":"Neurol Res","first-page":"690","article-title":"Ion channels and calcium signaling in cerebral arteries following subarachnoid hemorrhage","volume":"28","author":"Wellman","year":"2006"},{"key":"b38-jns091038","series-title":"Med Eng Phys","first-page":"169","article-title":"A novel device for in vitro isometric tension recordings of cylindrical artery segments","volume":"29","author":"Young","year":"2007"},{"key":"b39-jns091038","series-title":"Trends Pharmacol Sci","first-page":"38","article-title":"Widening potential for Ca2+ antagonists: non-L-type Ca2+ channel interaction","volume":"11","author":"Zernig","year":"1990"}],"container-title":["Journal of 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