Two-pore domain K channel, TASK-1, in pulmonary artery smooth muscle cells

被引:142
作者
Gurney, AM
Osipenko, ON
MacMillan, D
McFarlane, KM
Tate, RJ
Kempsill, FEJ
机构
[1] Univ Strathclyde, Dept Physiol & Pharmacol, Glasgow G4 0NR, Lanark, Scotland
[2] Quintiles Scotland Ltd, Edinburgh, Midlothian, Scotland
[3] Univ Glasgow, Inst Biomed & Life Sci, Glasgow, Lanark, Scotland
[4] Royal Alexandra Hosp, Argyll & Clyde NHS, Paisley, Renfrew, Scotland
关键词
two-pore domain K channel; pulmonary artery myocyte; smooth muscle; resting potential;
D O I
10.1161/01.RES.0000099883.68414.61
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Pulmonary vascular tone is strongly influenced by the resting membrane potential of smooth muscle cells, depolarization promoting Ca2+ influx, and contraction. The resting potential is determined largely by the activity of K+-selective ion channels, the molecular nature of which has been debated for some time. In this study, we provide strong evidence that the two-pore domain K+ channel, TASK-1, mediates a noninactivating, background K+ current (I-KN), which sets the resting membrane potential in rabbit pulmonary artery smooth muscle cells (PASMCs). TASK-1 mRNA was found to be present in PASMCs, and the membranes of PASMCs contained TASK-1 protein. Both I-KN and the resting potential were found to be exquisitely sensitive to extracellular pH, acidosis inhibiting the current and causing depolarization. Moreover, I-KN and the resting potential were enhanced by halothane (1 mmol/L), inhibited by Zn2+ (100 to 200 mumol/L) and anandamide (10 mumol/L), but insensitive to cytoplasmic Ca2+. These properties are all diagnostic of TASK-1 channels and add to previously identified features of I-KN that are shared with TASK-1, such as inhibition by hypoxia, low sensitivity to 4-aminopyridine and quinine and insensitivity to tetraethylammonium ions. It is therefore concluded that TASK-1 channels are major contributors to the resting potential in pulmonary artery smooth muscle. They are likely to play an important role in mediating pulmonary vascular responses to changes in extracellular pH, and they could be responsible for the modulatory effects of pH on hypoxic pulmonary vasoconstriction.
引用
收藏
页码:957 / 964
页数:8
相关论文
共 40 条
[1]   Effects of pH on vascular tension: Which are the important mechanisms? [J].
Aalkjaer, C ;
Poston, L .
JOURNAL OF VASCULAR RESEARCH, 1996, 33 (05) :347-359
[2]   Differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia [J].
Archer, SL ;
Huang, JMC ;
Reeve, HL ;
Hampl, V ;
Tolarova, S ;
Michelakis, E ;
Weir, EK .
CIRCULATION RESEARCH, 1996, 78 (03) :431-442
[3]   Block of the background K+ channel TASK-1 contributes to arrhythmogenic effects of platelet-activating factor [J].
Barbuti, A ;
Ishii, S ;
Shimizu, T ;
Robinson, RB ;
Feinmark, SJ .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2002, 282 (06) :H2024-H2030
[4]   TASK-1 is a highly modulated pH-sensitive 'leak' K+ channel expressed in brainstem respiratory neurons [J].
Bayliss, DA ;
Talley, EM ;
Sirois, JE ;
Lei, QB .
RESPIRATION PHYSIOLOGY, 2001, 129 (1-2) :159-174
[5]   EFFECTS OF ACIDOSIS AND ALKALOSIS ON HYPOXIC PULMONARY VASOCONSTRICTION IN DOGS [J].
BRIMIOULLE, S ;
LEJEUNE, P ;
VACHIERY, JL ;
LEEMAN, M ;
MELOT, C ;
NAEIJE, R .
AMERICAN JOURNAL OF PHYSIOLOGY, 1990, 258 (02) :H347-H353
[6]   An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells [J].
Buckler, KJ ;
Williams, BA ;
Honore, E .
JOURNAL OF PHYSIOLOGY-LONDON, 2000, 525 (01) :135-142
[7]   A novel O2-sensing mechanism in rat glossopharyngeal neurones mediated by a halothane-inhibitable background K+ conductance [J].
Campanucci, VA ;
Fearon, IM ;
Nurse, CA .
JOURNAL OF PHYSIOLOGY-LONDON, 2003, 548 (03) :731-743
[8]   Ca2+-activated Cl- currents in pulmonary arterial myocytes [J].
Clapp, LH ;
Turner, JL ;
Kozlowski, RZ .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1996, 270 (05) :H1577-H1584
[9]   OUTWARD CURRENTS IN RABBIT PULMONARY-ARTERY CELLS DISSOCIATED WITH A NEW TECHNIQUE [J].
CLAPP, LH ;
GURNEY, AM .
EXPERIMENTAL PHYSIOLOGY, 1991, 76 (05) :677-693
[10]   ATP-SENSITIVE K+ CHANNELS MEDIATE VASODILATION PRODUCED BY LEMAKALIM IN RABBIT PULMONARY-ARTERY [J].
CLAPP, LH ;
DAVEY, R ;
GURNEY, AM .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 264 (06) :H1907-H1915