Ca2+ entry and vasoconstriction during osmotic swelling of vascular smooth muscle cells.
Exposure of aortic strips from guinea-pigs to hypotonic extracellular fluid is followed by marked vasoconstriction, which is inhibited by D-600 (3 microM), a blocker of voltage-sensitive Ca2+ channels. Conventional electrophysiology, patch-clamp studies, pH determination with 2',7' bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF) and Ca2+ measurements with Fura-2 have been performed on smooth muscle cells cultured either from rat or human aorta to further elucidate the underlying mechanisms. Exposure of the cells to a 25% hypotonic extracellular fluid leads to a rapid and fully reversible depolarization, paralleled by an increase of the selectivity and conductance of the cell membrane to Cl-, an acidification of the cytoplasm and an increase of intracellular Ca2+ concentration ([Ca2+]i). The latter is inhibited by the Ca2+ channel blocker D-600 (1-3 microM). It is concluded that osmotic cell swelling leads to the activation of an anion channel. The subsequent depolarization of the cell membrane activates voltage-sensitive Ca2+ channels which increases [Ca2+]i, thus stimulating the contraction of vascular smooth muscle cells.
Lang
F
F
Physiologisches Institut der Universität Tübingen, Germany.
Busch
G L
GL
Zempel
G
G
Ditlevsen
J
J
Hoch
M
M
Emerich
U
U
Axel
D
D
Fingerle
J
J
Meierkord
S
S
Apfel
H
H
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D016257:Fura-2; D006168:Guinea Pigs; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D007038:Hypotonic Solutions; D016257:Fura-2