Diversity of response in vascular smooth muscle cells to changes in oxygen tension.
Hypoxia causes pulmonary vasoconstriction (HPV), but also dilation of systemic vessels and the ductus arteriosus. In the adult animal. HPV is initiated by inhibition of potassium current (IK) in the smooth muscle cells of small resistance arteries, which results in membrane depolarization and calcium entry through voltage-gated calcium channels. The oxygen-sensitive channels that initiate HPV are 4-aminopyridine (4-AP)-sensitive delayed rectifier channels (KDR), the most prominent of which has a conductance of 37 pS. In the fetus, hypoxia causes pulmonary vasoconstriction through inhibition of a calcium-sensitive potassium channel (KCa). In smooth muscle cells from the rabbit ductus arteriosus, which dilates in response to hypoxia, whole-cell potassium current is reversibly enhanced, rather than inhibited, by hypoxia. The principal oxygen-sensitive channel is inhibited by 4-AP and has a conductance of about 58 pS. There are morphological and electrophysiological differences between individual pulmonary artery smooth muscle cells, for example, in some cells IK is predominantly carried by KDR channels and in others by KCa channels. KDR cells are more common in the resistance pulmonary arteries and KCa in the conduit arteries. Responses of specific vessels (conduit, resistance; pulmonary, systemic, ductus) at different stages of development (fetal, neonatal and adult) to changes in oxygen tension may be determined by the distribution of a variety of ion channels in the smooth muscle cells.
Weir
E K
EK
Department of Medicine, VA Medical Center, Minneapolis, Minnesota, USA.
Reeve
H L
HL
Cornfield
D N
DN
Tristani-Firouzi
M
M
Peterson
D A
DA
Archer
S L
SL
D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology; D004373:Ductus Arteriosus / Q000378:metabolism; D005260:Female; D005311:Fetal Hypoxia / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D015640:Ion Channel Gating; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D011247:Pregnancy; D011651:Pulmonary Artery / Q000378:metabolism; D011652:Pulmonary Circulation; D011817:Rabbits; D051381:Rats; D012756:Sheep; D014661:Vasoconstriction
D015221:Potassium Channels; D010100:Oxygen