Details

Autor(en) / Beteiligte

• Yuan, Xiao-Jian
• Wang, Jian
• Juhaszova, Magdalena
• Golovina, Vera A
• Rubin, Lewis J

Titel

Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells

Ist Teil von

• American journal of physiology. Lung cellular and molecular physiology, 1998-04, Vol.274 (4), p.621-L635

Ort / Verlag

United States

Erscheinungsjahr

1998

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 1  Division of Pulmonary and Critical Care Medicine, Department of Medicine, and 2  Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201 K + -channel activity-mediated alteration of the membrane potential and cytoplasmic free Ca 2+ concentration ([Ca 2+ ] cyt ) is a pivotal mechanism in controlling pulmonary vasomotor tone. By using combined approaches of patch clamp, imaging fluorescent microscopy, and molecular biology, we examined the electrophysiological properties of K + channels and the role of different K + currents in regulating [Ca 2+ ] cyt and explored the molecular identification of voltage-gated K + (K V )- and Ca 2+ -activated K + (K Ca )-channel genes expressed in pulmonary arterial smooth muscle cells (PASMC). Two kinetically distinct K V currents [ I K(V) ], a rapidly inactivating (A-type) and a noninactivating delayed rectifier, as well as a slowly activated K Ca current [ I K(Ca) ] were identified. I K(V) was reversibly inhibited by 4-aminopyridine (5 mM), whereas I K(Ca) was significantly inhibited by charybdotoxin (10-20 nM). K + channels are composed of pore-forming -subunits and auxiliary -subunits. Five K V -channel -subunit genes from the Shaker subfamily (K V 1.1, K V 1.2, K V 1.4, K V 1.5, and K V 1.6), a K V -channel -subunit gene from the Shab subfamily (K V 2.1), a K V -channel modulatory -subunit (K V 9.3), and a K Ca -channel -subunit gene ( rSlo ), as well as three K V -channel -subunit genes (K V 1.1, K V 2, and K V 3) are expressed in PASMC. The data suggest that 1 ) native K + channels in PASMC are encoded by multiple genes; 2 ) the delayed rectifier I K(V) may be generated by the K V 1.1, K V 1.2, K V 1.5, K V 1.6, K V 2.1, and/or K V 2.1/K V 9.3 channels; 3 ) the A-type I K(V) may be generated by the K V 1.4 channel and/or the delayed rectifier K V channels (K V 1 subfamily) associated with -subunits; and 4 ) the I K(Ca) may be generated by the rSlo gene product. The function of the K V channels plays an important role in the regulation of membrane potential and [Ca 2+ ] cyt in PASMC. potassium channel; polymerase chain reaction; fluorescence microscopy; patch clamp; cytoplasmic calcium