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Swelling‐activated cation channels mediate depolarization of rat cerebrovascular smooth muscle by hyposmolarity and intravascular pressure
Author(s) -
Welsh Donald G.,
Nelson Mark T.,
Eckman Delrae M.,
Brayden Joseph E.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.t01-1-00139.x
Subject(s) - depolarization , dids , vascular smooth muscle , biophysics , chemistry , reversal potential , swelling , medicine , patch clamp , biochemistry , smooth muscle , biology , receptor , pathology , membrane
1 Increases in intravascular pressure depolarize vascular smooth muscle cells. Based on the attenuating effects of Cl − channel antagonists, it has been suggested that swelling‐activated Cl − channels may be integral to this response. Consequently, this study tested for the presence of a swelling‐activated Cl − conductance in both intact rat cerebral arteries and isolated rat smooth muscle cells. 2 A 50 mosmol l −1 hyposmotic challenge (300 to 250 mosmol l −1 ) constricted rat cerebral arteries. This constriction contained all the salient features of a pressure‐induced response including smooth muscle cell depolarization and a rise in intracellular Ca 2+ that was blocked by voltage‐operated Ca 2+ channel antagonists. The hyposmotically induced depolarization was attenuated by DIDS (300 μ m ) and tamoxifen (1 μ m ), a response consistent with the presence of a swelling‐activated Cl − conductance. 3 A swelling‐activated current was identified in cerebral vascular smooth muscle cells. This current was sensitive to Cl − channel antagonists including DIDS (300 μ m ), tamoxifen (1 μ m ) and IAA‐94 (100 μ m ). However, contrary to expectations, the reversal potential of this swelling‐activated current shifted with the Na + equilibrium potential and not the Cl − equilibrium potential, indicating that the swelling‐activated current was carried by cations and not anions. The swelling‐activated cation current was blocked by Gd 3+ , a cation channel antagonist. 4 Gd 3+ also blocked both swelling‐ and pressure‐induced depolarization of smooth muscle cells in intact cerebral arteries. 5 These findings suggest that swelling‐ and pressure‐induced depolarization arise from the activation of a cation conductance. This current is inhibited by DIDS, tamoxifen, IAA‐94 and gadolinium.