Abstract：
:In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K+) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting IKur, the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting IK,ACh, the Ca2+-activated K+ channels of small conductance (SK) conducting ISK, and the two-pore domain K+ (K2P) channels (tandem of P domains, weak inward-rectifying K+ channels (TWIK-1), TWIK-related acid-sensitive K+ channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents ITWIK-1, ITASK-1, and ITASK-3. Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.
journal_name
Can J Physiol Pharmacoljournal_title
Canadian journal of physiology and pharmacologyauthors
Ravens Udoi
10.1139/cjpp-2017-0024subject
Has Abstractpub_date
2017-11-01 00:00:00pages
1313-1318issue
11eissn
0008-4212issn
1205-7541journal_volume
95pub_type
杂志文章,评审abstract：:In the present study we characterized the receptor(s) that mediates non-adrenergic non-cholinergic (NANC) contractions of isolated guinea pig cervical trachea, using CP-99,994, a selective neurokinin (NK1) receptor antagonist, and SR-48,968, a selective neurokinin (NK2) receptor antagonist. The activity of these two a...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y94-028
更新日期：1994-02-01 00:00:00
abstract：:In experiments on isolated guinea pig papillary muscles the effects of verapamil (5 mg/L) and caffeine (1 g/L) on the two-component contraction were investigated. The muscles were continuously superfused with normal Tyrode's solution containing 2 mg of noradrenaline/L at 20--22 degrees C. The first derivative of contr...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y79-132
更新日期：1979-08-01 00:00:00
abstract：:Opioid and N-methyl-d-aspartate (NMDA) receptors mediate different effects of fluoxetine. We investigated whether opioid and NMDA receptors are involved in the protective effect of fluoxetine against the behavioral despair induced by acute physical stress in male mice. We used the forced swimming test (FST), tail susp...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2015-0429
更新日期：2016-06-01 00:00:00
abstract：:Calcium-activated chloride channels (ClCa) are ligand-gated anion channels as they have been shown to be activated by a rise in intracellular Ca2+ concentration in various cell types including cardiac, skeletal and vascular smooth muscle cells, endothelial and epithelial cells, as well as neurons. Because ClCa channel...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y05-040
更新日期：2005-07-01 00:00:00
abstract：:ARHGAP21 is a Rho-GAP that controls GTPases activity in several tissues, but its role on liver lipid metabolism is unknown. Thus, to achieve the Rho-GAP role in the liver, control and ARHGAP21-haplodeficient mice were fed chow (Ctl and Het) or high-fat diet (Ctl-HFD and Het-HFD) for 12 weeks, and pyruvate and insulin ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2018-0691
更新日期：2019-11-01 00:00:00
abstract：:Altered sympathetic nervous activity has been linked to the development and persistence of obesity, partly relating to overfeeding. Binding of the selective, positron-emitting phosphodiesterase-4 (PDE4) inhibitor (R)-[11C]rolipram provides a direct index of the cAMP-hydrolyzing enzyme PDE4. This study examines progres...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y09-001
更新日期：2009-03-01 00:00:00
abstract：:Modification of the mouse interstitial cell testosterone assay by the addition of 1.5 microM forskolin to the incubation medium has improved the sensitivity of this luteinizing hormone bioassay from approximately 100 to 3 pg/tube of NIH rLH RP-2. Luteinizing hormone can be clearly detected in 1 microL of serum from ra...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y92-116
更新日期：1992-06-01 00:00:00
abstract：:Heme plays a critical role in blood pressure regulation because it is required by a number of enzymes that synthesize vascular modulators, including nitric oxide (NO), carbon monoxide (CO), guanosine 3',5'-cyclic monophosphate (cGMP), endothelium-derived hyperpolarizing factor (EDHF), and prostacyclin. The goal of thi...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y08-064
更新日期：2008-09-01 00:00:00
abstract：:Wound healing is important for longevity. Midkine is a cytokine involved in controlling tissue repair and new tissue development, and in regulating inflammation. We investigated the effect of midkine on wound healing in rats. In total, 108 Wistar albino rats were used: 12 as healthy and diabetic controls; 96 were spli...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/cjpp-2016-0439
更新日期：2017-05-01 00:00:00
abstract：:A brief burst of electrical stimuli delivered to the vagus nerve during the cardiac cycle elicits a triphasic cardiac chronotropic response. The cardiac cycle length initially increases, then briefly decreases, and subsequently increases again. We studied the effects of a calcium channel blocking agent, verapamil, on ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y86-164
更新日期：1986-07-01 00:00:00
abstract：:Total renal blood flow, glomerular filtration rate, and renal excretory function were determined in anesthetized rats treated with intravenous infusion of ethacrynic acid, 0.36 mg.min-1.kg-1, alone or in combination with cysteine. Simultaneously, the corticomedullary electrolyte gradient was evaluated in vivo from mea...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y90-191
更新日期：1990-09-01 00:00:00
abstract：:Aside from its established immunologic and hematologic functions, the spleen also plays an important role in cardiovascular regulation. This occurs through changes in intrasplenic microvascular tone, as well as through splenic neurohormonal modulation of the renal and mesenteric vascular beds. Splenic regulation of bl...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/Y08-103
更新日期：2009-01-01 00:00:00
abstract：:Aortas were removed from six mature lambs and four sheep and pressure fixed at 100 and 120 mmHg pressure (1 mmHg = 133.322 Pa), respectively, in 10% buffered formalin. The numbers of elastin layers were counted from cross sections at different distances down the aorta, from the distal arch to the iliac bifurcation, an...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y83-016
更新日期：1983-02-01 00:00:00
abstract：:The present paper reviews current knowledge of the development and plasticity of the inhibitory gamma-aminobutyric acid (GABA) containing circuitry of the cerebral neocortex, in particular, the rat somatosensory barrel field cortex. Recent studies reveal a delayed and protracted maturation of the inhibitory compared w...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：
更新日期：1997-05-01 00:00:00
abstract：:The ability of the heart to respond to adrenergic stimulation diminishes with aging, and this may be one of the factors contributing to the age-associated decline in cardiac stress responsiveness. On the other hand, little is known about the impact of aging on the responsiveness of the heart to cholinergic stimulation...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y92-232
更新日期：1992-12-01 00:00:00
abstract：:The ability of human skeletal muscle to provide anaerobically derived ATP during short-term, intense activity is examined. The paper emphasizes the information obtained from direct measurements of substrates, intermediates, and products of the pathways in muscle that provide anaerobically derived ATP. The capacity of ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y92-023
更新日期：1992-01-01 00:00:00
abstract：:Cardiac adenosine receptors are coupled to adenylate cyclase inhibition. In the guinea pig heart, the relative agonist potencies observed for adenylate cyclase inhibition were R-N6-phenylisopropyladenosine (R-PIA) = N6-cyclohexyladenosine greater than 5'-N-ethylcarboxamidoadenosine much greater than S-PIA. In both atr...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y86-252
更新日期：1986-12-01 00:00:00
abstract：:Ten minutes after KCl-depolarization of rat myometrial strips, at which time the muscles were in a state of sustained contracture, tissue levels of adenosine 3',5'-cyclic monophosphate (cyclic AMP) were increased by approximately 40% over relaxed controls, and levels of guanosine 3',5'-cyclic monophosphate (cyclic GMP...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y75-153
更新日期：1975-12-01 00:00:00
abstract：:Since human thermoregulation at rest is altered by cold exposure, it was hypothesized that physical training under cold conditions would alter thermoregulation. Three groups (n = 8) of male subjects (mean age 24.3 +/- 0.9 years) were evaluated: group T (interval training at 21 degrees C), group CT (interval training a...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y02-109
更新日期：2002-09-01 00:00:00
abstract：:In the rat, prolonged enteral or parenteral alimentation with a high-carbohydrate diet results in hyperinsulinemia, which is substantially greater with the parenteral route. Supplementing the parenteral infusate with porcine gastric inhibitory polypeptide (GIP) to approximate plasma immunoreactive GIP levels achieved ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y89-175
更新日期：1989-09-01 00:00:00
abstract：:Our objective was to investigate the effects of chronic excess iodine intake on thyroid functions and thyroid oxidative stress state in hypothyroid rats. Sixty rats were divided into euthyroid and hypothyroid (thiocyanate-induced) groups with or without administration of excess iodine (3000 or 6000 μg/L) for 8 weeks. ...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y2012-046
更新日期：2012-05-01 00:00:00
abstract：:The effects of two structurally similar pyrazine derivatives, tetramethylpyrazine (TMP) and tetraethylpyrazine (TEP) on the contractile responses of dog saphenous vein to KCl (via membrane depolarization), phenylephrine (PHE, alpha 1-adrenergic agonist), and B-HT 920 (alpha 2-adrenergic agonist) were investigated. The...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y91-173
更新日期：1991-08-01 00:00:00
abstract：:A major limitation of the use of organic nitrates in cardiovascular medicine is the development of tolerance, which has been attributed, in part, to a decrease in their metabolic activation in the vascular smooth muscle cell. Recently, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) was shown to potentiate vascu...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：2001-01-01 00:00:00
abstract：:Structural analysis of G-protein-coupled receptors has largely been limited to photoaffinity labeling and site-directed mutagenesis. This is primarily due to the difficulty in the production of antibodies against this class of receptors. We were therefore interested in tagging the amino-terminal side of the human angi...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：
更新日期：1997-06-01 00:00:00
abstract：:To determine if increased endometrial vascular permeability (a response which precedes decidualization) could be obtained in temporally nonsensitized uteri by treatments designed to increase endometrial adenosine 3':5'-cyclic monophosphate (cAMP) concentrations, cholera toxin (an activator of adenylate cyclase) was in...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y85-172
更新日期：1985-09-01 00:00:00
abstract：:This paper presents data showing that the sympathetic autonomic areas of the cat thoracolumbar spinal cord contain nerve terminals and fibres with immunoreactivity for at least seven neuropeptides. The distribution in the intermediolateral cell column of the terminals and fibres which contain enkephalin-, neuropeptide...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章,评审
doi：10.1139/y87-254
更新日期：1987-08-01 00:00:00
abstract：:The effects of estrogen and progesterone domination, achieved by administering estrogen (E) and estrogen plus progesterone (E + P), on rat uterine reactivity to Ca2+ and to Ca2+ channel ligands (antagonist and activator) were compared. The inhibitory activities of nifedipine, diltiazem, and D 600 against K+ depolariza...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y87-327
更新日期：1987-10-01 00:00:00
abstract：:Strips of rabbit thoracic aorta precontracted with phenylephrine relaxed when exposed to selected synthetic peptides derived from the cell attachment domain of fibronectin. The relaxations elicited by both acetylcholine and the hexapeptide Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) were dependent on the presence of an intact en...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y88-118
更新日期：1988-06-01 00:00:00
abstract：:Rats fed a polychlorinated biphenyl (PCB) mixture in a high- or low-iodine diet (HID or LID respectively) for 15 days had thyroid enlargement, low serum thyroxine (T4), and high serum thyrotropin concentrations. Although binding of thyroid hormones to serum proteins was reduced in PCB-fed animals, the free T4 index (r...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 杂志文章
doi：10.1139/y77-041
更新日期：1977-04-01 00:00:00
abstract：:This Symposium includes 15 presentations and an editorial review dealing with prorenin activation and function. It comes 20 years after prorenin was first reported in various contexts and attracted attention because of its connection with renin--angiotensin, its high concentration relative to renin in the blood, and i...
journal_title：Canadian journal of physiology and pharmacology
pub_type： 社论,评审
doi：10.1139/y91-193
更新日期：1991-09-01 00:00:00
