Forebrain HCN1 channels contribute to hypnotic actions of ketamine.

Abstract:

BACKGROUND:Ketamine is a commonly used anesthetic, but the mechanistic basis for its clinically relevant actions remains to be determined. The authors previously showed that HCN1 channels are inhibited by ketamine and demonstrated that global HCN1 knockout mice are twofold less sensitive to hypnotic actions of ketamine. Although that work identified HCN1 channels as a viable molecular target for ketamine, it did not determine the relevant neural substrate. METHODS:To localize the brain region responsible for HCN1-mediated hypnotic actions of ketamine, the authors used a conditional knockout strategy to delete HCN1 channels selectively in excitatory cells of the mouse forebrain. A combination of molecular, immunohistochemical, and cellular electrophysiologic approaches was used to verify conditional HCN1 deletion; a loss-of-righting reflex assay served to ascertain effects of forebrain HCN1 channel ablation on hypnotic actions of ketamine. RESULTS:In conditional knockout mice, HCN1 channels were selectively deleted in cortex and hippocampus, with expression retained in cerebellum. In cortical pyramidal neurons from forebrain-selective HCN1 knockout mice, effects of ketamine on HCN1-dependent membrane properties were absent; notably, ketamine was unable to evoke membrane hyperpolarization or enhance synaptic inputs. Finally, the EC50 for ketamine-induced loss-of-righting reflex was shifted to significantly higher concentrations (by approximately 31%). CONCLUSIONS:These data indicate that forebrain principal cells represent a relevant neural substrate for HCN1-mediated hypnotic actions of ketamine. The authors suggest that ketamine inhibition of HCN1 shifts cortical neuron electroresponsive properties to contribute to ketamine-induced hypnosis.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Zhou C,Douglas JE,Kumar NN,Shu S,Bayliss DA,Chen X

doi

10.1097/ALN.0b013e318287b7c8

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

785-95

issue

4

eissn

0003-3022

issn

1528-1175

journal_volume

118

pub_type

杂志文章
  • Ethanol and contraction of venous smooth muscle.

    abstract::Low concentrations of ethanol (17 mM) inhibited development of spontaneous mechanical activity (vasomotion) in isolated rat portal veins. Low concentrations of ethanol potentiated, however, contractions induced by epinephrine, but not those induced by angiotensin or potassium. Higher concentrations of ethanol, such as...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-197604000-00009

    authors: Edgarian H,Altura BM

    更新日期:1976-04-01 00:00:00

  • Role of monitoring devices in prevention of anesthetic mishaps: a closed claims analysis.

    abstract::Anesthesiologist-reviewers examined 1,175 anesthetic-related closed malpractice claims from 17 professional liability insurance companies. The claims were filed between 1974 and 1988. The reviewers were asked to determine if the negative outcome was preventable by proper use of additional monitoring devices available ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-198910000-00010

    authors: Tinker JH,Dull DL,Caplan RA,Ward RJ,Cheney FW

    更新日期:1989-10-01 00:00:00

  • Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery.

    abstract::The goal of this randomized study of high-risk surgical patients was to determine whether intraoperative thoracic epidural anesthesia in combination with light general anesthesia alters postoperative morbidity when compared to a standard technique of "balanced" general anesthesia. A total of 173 patients scheduled for...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00000542-199110000-00010

    authors: Baron JF,Bertrand M,Barré E,Godet G,Mundler O,Coriat P,Viars P

    更新日期:1991-10-01 00:00:00

  • Ventilatory effects of dexmedetomidine, atipamezole, and isoflurane in dogs.

    abstract::Dexmedetomidine (DMED) is a novel alpha 2 adrenergic agonist that has been shown to have potent analgesic and anesthetic sparing effects. This study was designed to investigate the effects of DMED, both alone and combined with isoflurane, on resting ventilation, the hypercapnic response, and the hypoxic response in do...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199204000-00014

    authors: Nguyen D,Abdul-Rasool I,Ward D,Hsieh J,Kobayashi D,Hadlock S,Singer F,Bloor B

    更新日期:1992-04-01 00:00:00

  • Differential effects of fentanyl and morphine on intracellular Ca2+ transients and contraction in rat ventricular myocytes.

    abstract:BACKGROUND:Our objective was to elucidate the direct effects of fentanyl and morphine on cardiac excitation-contraction coupling using individual, field-stimulated rat ventricular myocytes. METHODS:Freshly isolated myocytes were loaded with fura-2 and field stimulated (0.3 Hz) at 28 degrees C. Amplitude and timing of ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199812000-00033

    authors: Kanaya N,Zakhary DR,Murray PA,Damron DS

    更新日期:1998-12-01 00:00:00

  • Propofol: its role in changing the practice of anesthesia.

    abstract::Pharmacokinetics and pharmacodynamics of propofol infusions during general anesthesia. By Audrey Shafer, Van A. Doze, Steven L. Shafer, and Paul F. White. Anesthesiology 1988; 69:348-56. Reprinted with permission.The pharmacokinetic and pharmacodynamic properties of propofol (Diprivan) were studied in 50 elective surg...

    journal_title:Anesthesiology

    pub_type: 古典文章,评论,杂志文章

    doi:10.1097/ALN.0b013e31818ddba8

    authors: White PF

    更新日期:2008-12-01 00:00:00

  • Diagnosis of ventilator-associated pneumonia: an evaluation of direct examination and presence of intracellular organisms.

    abstract:BACKGROUND:Ventilator-associated pneumonia (VAP) requires early diagnosis and adequate antibiotic therapy. The aim of this prospective postmortem study was to assess the accuracy of direct examination and quantification of intracellular organisms (ICO) for the diagnosis of VAP. METHODS:Total and differential cell coun...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199708000-00013

    authors: Papazian L,Autillo-Touati A,Thomas P,Bregeon F,Garbe L,Saux P,Seite R,Gouin F

    更新日期:1997-08-01 00:00:00

  • Effects of thoracic epidural anesthesia with and without autonomic nervous system blockade on cardiac monophasic action potentials and effective refractoriness in awake dogs.

    abstract:BACKGROUND:The effects of thoracic epidural anesthesia (TEA) on myocardial repolarization and arrhythmogenicity are only incompletely understood. This is primarily because of the lack of appropriate experimental models. In most of the studies performed thus far, TEA was used in anesthetized animals. Baseline anesthesia...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200107000-00023

    authors: Meissner A,Eckardt L,Kirchhof P,Weber T,Rolf N,Breithardt G,Van Aken H,Haverkamp W

    更新日期:2001-07-01 00:00:00

  • Protective effect of hypothermia in cerebral oxygen deficiency caused by arterial hypoxia.

    abstract::To study the cerebral protective effects of hypothermia in arterial hypoxia, anesthetized (70% N2O), mechanically ventilated rats were cooled to a body temperature of 27 C. Hypoxia was induced by decreasing the oxygen content in the inspired gas mixture either to 6-7 per cent or to 2.5-3 per cent. This reduced mean Pa...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-197601000-00006

    authors: Carlsson C,Hägerdal M,Siesjö BK

    更新日期:1976-01-01 00:00:00

  • Isozyme-specific effects of protein kinase C in pain modulation.

    abstract:BACKGROUND:Protein kinase C (PKC) is a family of serine/threonine kinases that contains more than 10 isozymes. Evidence suggests that PKC may play important roles in pain modulation, but the isozyme-specific effects of PKC on different aspects of pain modulation are not fully understood. We hypothesize that different P...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/ALN.0b013e3182390788

    authors: Zhao C,Leitges M,Gereau RW 4th

    更新日期:2011-12-01 00:00:00

  • Substance Use Disorder in Physicians after Completion of Training in Anesthesiology in the United States from 1977 to 2013.

    abstract:BACKGROUND:Substance use disorder among physicians can expose both physicians and their patients to significant risk. Data regarding the epidemiology and outcomes of physician substance use disorder are scarce but could guide policy formulation and individual treatment decisions. This article describes the incidence an...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/ALN.0000000000003310

    authors: Warner DO,Berge K,Sun H,Harman A,Wang T

    更新日期:2020-08-01 00:00:00

  • Halothane changes the relationships between lung resistances and lung volume.

    abstract::The authors hypothesized that relaxation of airway smooth muscle by halothane lessens the dependence of airway resistance on lung volume, and that halothane alters the relationship between pulmonary resistance and lung volume by changing both the airway and tissue components of pulmonary resistance. The relationship a...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199202000-00012

    authors: Joyner MJ,Warner DO,Rehder K

    更新日期:1992-02-01 00:00:00

  • Impaired systolic thickening associated with halothane in the presence of a coronary stenosis is mediated by changes in hemodynamics.

    abstract::Myocardial ischemia results when halothane is administered to animals with severe coronary stenosis. This study was done to separate the effect of halothane, per se, on myocardial ischemia from indirect cardiovascular effects, primarily hypotension, that might cause ischemia by altering the oxygen supply-demand balanc...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-198605000-00014

    authors: Buffington CW

    更新日期:1986-05-01 00:00:00

  • Variations in pancuronium requirement, plasma concentration, and urinary excretion induced by cardiopulmonary bypass with hypothermia.

    abstract::To determine the effects of cardiopulmonary bypass (CPB) and hypothermia on the neuromuscular blockade produced by pancuronium, this relaxant was infused intravenously into 10 anesthetized patients to produce and maintain 90% depression of the twitch tension of the adductor pollicis muscle following supramaximal ulnar...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-198306000-00004

    authors: d'Hollander AA,Duvaldestin P,Henzel D,Nevelsteen M,Bomblet JP

    更新日期:1983-06-01 00:00:00

  • Redistribution of microcirculatory blood flow within the intestinal wall during sepsis and general anesthesia.

    abstract:BACKGROUND:Hypoperfusion of the intestinal mucosa remains an important clinical problem during sepsis. Impairment of the autoregulation of microcirculatory blood flow in the intestinal tract has been suggested to play an important role in the development of multiple organ failure during sepsis and surgery. The authors ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200303000-00014

    authors: Hiltebrand LB,Krejci V,tenHoevel ME,Banic A,Sigurdsson GH

    更新日期:2003-03-01 00:00:00

  • Effect of alpha2B-adrenoceptor polymorphism on peripheral vasoconstriction in healthy volunteers.

    abstract:BACKGROUND:Alpha-2B adrenoceptor is the vasoconstrictive subtype in the mouse. Human alpha2B-AR deletion (D) allele has been associated with loss of short-term agonist-promoted receptor desensitization, which may lead to increased vasoconstriction on alpha2 activation. The goal of this study was to test the hypothesis ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200503000-00010

    authors: Talke P,Stapelfeldt C,Lobo E,Brown R,Scheinin M,Snapir A

    更新日期:2005-03-01 00:00:00

  • Obesity in diabetic patients undergoing coronary artery bypass graft surgery is associated with increased postoperative morbidity.

    abstract:BACKGROUND:Despite the fact that obesity is a known risk factor for cardiovascular disease, many studies have failed to demonstrate that obesity is independently associated with an increased risk of cardiovascular morbidity and mortality in nondiabetic patients undergoing coronary artery bypass graft surgery. The autho...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200603000-00010

    authors: Pan W,Hindler K,Lee VV,Vaughn WK,Collard CD

    更新日期:2006-03-01 00:00:00

  • Differentiating Drug-related and State-related Effects of Dexmedetomidine and Propofol on the Electroencephalogram.

    abstract:BACKGROUND:Differentiating drug-related changes and state-related changes on the electroencephalogram during anesthetic-induced unconsciousness has remained a challenge. To distinguish these, we designed a rigorous experimental protocol with two drugs known to have distinct molecular mechanisms of action. We hypothesiz...

    journal_title:Anesthesiology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/ALN.0000000000002192

    authors: Scheinin A,Kallionpää RE,Li D,Kallioinen M,Kaisti K,Långsjö J,Maksimow A,Vahlberg T,Valli K,Mashour GA,Revonsuo A,Scheinin H

    更新日期:2018-07-01 00:00:00

  • Continuous interscalene analgesia with ropivacaine 2 mg/ml after major shoulder surgery.

    abstract:BACKGROUND:In this open, randomized study, the pharmacokinetics, clinical efficacy, and safety of a 48-h continuous interscalene infusion of 2 mg/ml ropivacaine for postoperative pain relief were investigated in patients undergoing open major shoulder surgery. METHODS:An initial interscalene block with 30 ml ropivacai...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00000542-200301000-00023

    authors: Ekatodramis G,Borgeat A,Huledal G,Jeppsson L,Westman L,Sjövall J

    更新日期:2003-01-01 00:00:00

  • Pulmonary blood flow redistribution with low levels of positive end-expiratory pressure.

    abstract:BACKGROUND:Recent studies have questioned the importance of the gravitational model of pulmonary perfusion. Because low levels of positive end-expiratory pressure (PEEP) are commonly used during anesthesia, the authors studied the distribution of pulmonary blood flow with low levels of PEEP using a high spatial resolut...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199805000-00021

    authors: Kallas HJ,Domino KB,Glenny RW,Anderson EA,Hlastala MP

    更新日期:1998-05-01 00:00:00

  • Direct evidence for the ongoing brain activation by enhanced dynorphinergic system in the spinal cord under inflammatory noxious stimuli.

    abstract:BACKGROUND:Dynorphin A in the spinal cord is considered to contribute to nociceptive stimuli. However, it has not yet been determined whether activation of the spinal dynorphinergic system under nociceptive stimuli plays a role in direct acceleration of the ascending nociceptive pathway. In this study, the authors inve...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/ALN.0b013e3181ca31d9

    authors: Taketa Y,Niikura K,Kobayashi Y,Furuya M,Shimizu T,Narita M,Imai S,Kuzumaki N,Maitani Y,Yamazaki M,Inada E,Iseki M,Suzuki T,Narita M

    更新日期:2010-02-01 00:00:00

  • Thiopental pharmacokinetics under conditions of long-term infusion.

    abstract::Thiopental was used in long-term infusion (3-4.5 mg . kg-1 . h-1 during 4-8 days) to protect the brain from injury following trauma. Thiopental plasma concentrations were measured during infusion (48 patients) and after infusion (14 patients) to determine the kinetics of the drug in continuous infusion. All mean value...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-198507000-00007

    authors: Turcant A,Delhumeau A,Premel-Cabic A,Granry JC,Cottineau C,Six P,Allain P

    更新日期:1985-07-01 00:00:00

  • Positive experimental demonstration of the negative brain "protective" effects of anesthetics following cardiac arrest.

    abstract::The cerebral metabolic effects of a massive dose of thiopental (177 mg/kg) were investigated in seven dogs. The systemic circulation was supported with an extracorporeal circuit. At an infusion rate of 2 mg/kg/min, cerebral oxygen consumption (CMR(O(2))) decreased progressively until cerebral electrical silence was pr...

    journal_title:Anesthesiology

    pub_type: 评论,杂志文章

    doi:10.1097/00000542-200210000-00036

    authors: Michenfelder JD

    更新日期:2002-10-01 00:00:00

  • Sepsis is associated with a preferential diaphragmatic atrophy: a critically ill patient study using tridimensional computed tomography.

    abstract:BACKGROUND:Diaphragm and psoas are affected during sepsis in animal models. Whether diaphragm or limb muscle is preferentially affected during sepsis in the critically ill remains unclear. METHODS:Retrospective secondary analysis study including 40 patients, comparing control (n = 17) and critically ill patients, with...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/ALN.0000000000000201

    authors: Jung B,Nougaret S,Conseil M,Coisel Y,Futier E,Chanques G,Molinari N,Lacampagne A,Matecki S,Jaber S

    更新日期:2014-05-01 00:00:00

  • Transcutaneous cardiac pacing during thoracic surgery. Feasibility and hemodynamic evaluation by transesophageal echocardiography.

    abstract:BACKGROUND:Occasionally, emergency perioperative pacing is necessary. Transcutaneous cardiac pacing is noninvasive, safe, and readily available. Its feasibility and hemodynamic effects during thoracic surgery and one-lung ventilation have not been established. METHODS:Twenty anesthetized patients (aged 25-70 yr) witho...

    journal_title:Anesthesiology

    pub_type: 临床试验,杂志文章

    doi:10.1097/00000542-199310000-00013

    authors: Amar D,Gross JN,Burt M,Schwinger ME,Rusch VW,Reinsel RA

    更新日期:1993-10-01 00:00:00

  • Development and validation of a risk quantification index for 30-day postoperative mortality and morbidity in noncardiac surgical patients.

    abstract:BACKGROUND:Optimal risk adjustment is a requisite precondition for monitoring quality of care and interpreting public reports of hospital outcomes. Current risk-adjustment measures have been criticized for including baseline variables that are difficult to obtain and inadequately adjusting for high-risk patients. The a...

    journal_title:Anesthesiology

    pub_type: 杂志文章,随机对照试验

    doi:10.1097/ALN.0b013e318219d5f9

    authors: Dalton JE,Kurz A,Turan A,Mascha EJ,Sessler DI,Saager L

    更新日期:2011-06-01 00:00:00

  • Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration.

    abstract::Desflurane (formerly I-653) is a new inhalaticnal anesthetic with a promising pharmacokinetic profile that includes low solubility in blood and tissue, including fat. Since its lipid solubility is less than that of other volatile agents, it may have lower potency. Low solubility would be expected to increase the rate ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199103000-00007

    authors: Rampil IJ,Lockhart SH,Zwass MS,Peterson N,Yasuda N,Eger EI 2nd,Weiskopf RB,Damask MC

    更新日期:1991-03-01 00:00:00

  • Inhaled nitric oxide selectively decreases pulmonary vascular resistance without impairing oxygenation during one-lung ventilation in patients undergoing cardiac surgery.

    abstract:BACKGROUND:Inhaled nitric oxide (NO), an endothelium-derived relaxing factor, is a selective pulmonary vasodilator. The authors investigated whether inhaled NO decreases pulmonary vascular resistance (PVR) while preserving hypoxic pulmonary vasoconstriction and whether it maintains or improves oxygenation in patients d...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:

    authors: Rich GF,Lowson SM,Johns RA,Daugherty MO,Uncles DR

    更新日期:1994-01-01 00:00:00

  • Involvement of Ca2+ sensitization in ropivacaine-induced contraction of rat aortic smooth muscle.

    abstract:BACKGROUND:The mechanisms of amino-amide local anesthetic agent-induced vasoconstriction remain unclear. The current study was designed to examine the roles of the protein kinase C (PKC), Rho kinase, and p44/42 mitogen-activated protein kinase (p44/42 MAPK) signaling pathways in calcium (Ca2+)-sensitization mechanisms ...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-200509000-00018

    authors: Yu J,Tokinaga Y,Kuriyama T,Uematsu N,Mizumoto K,Hatano Y

    更新日期:2005-09-01 00:00:00

  • Insufflated halothane increases venous admixture less than nitroprusside in canine atelectasis.

    abstract::Although it generally is agreed that halothane is a pulmonary vasodilator, its effect on venous admixture and hypoxic pulmonary vasoconstriction are more controversial. The effects of 2.4% halothane on pulmonary vascular resistance and venous admixture were investigated in an isolated canine lobe made atelectatic. Hal...

    journal_title:Anesthesiology

    pub_type: 杂志文章

    doi:10.1097/00000542-199208000-00013

    authors: Johnson D,Hurst T,Mayers I

    更新日期:1992-08-01 00:00:00