Ionic mechanism for contractile response to hyposmotic challenge in canine basilar arteries.
A hyposmotic challenge elicited contraction of isolated canine basilar arteries. The contractile response was nearly abolished by the removal of extracellular Ca(2+) and by the voltage-dependent Ca(2+) channel (VDCC) blocker nicardipine, but it was unaffected by thapsigargin, which depletes intracellular Ca(2+) stores. The contraction was also inhibited by Gd(3+) and ruthenium red, cation channel blockers, and Cl(-) channel blockers DIDS and niflumic acid. The reduction of extracellular Cl(-) concentrations enhanced the hypotonically induced contraction. Patch-clamp analysis showed that a hyposmotic challenge activated outwardly rectifying whole cell currents in isolated canine basilar artery myocytes. The reversal potential of the current was shifted toward negative potentials by reductions in intracellular Cl(-) concentration, indicating that the currents were carried by Cl(-). Moreover, the currents were abolished by 10 mM BAPTA in the pipette solution and by the removal of extracellular Ca(2+). Taken together, these results suggest that a hyposmotic challenge activates cation channels, which presumably cause Ca(2+) influx, thereby activating Ca(2+)-activated Cl(-) channels. The subsequent membrane depolarization is likely to increase Ca(2+) influx through VDCC and elicit contraction.
Yano
Shunsuke
S
Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka City, Shizuoka 422-8526, Japan.
Ishikawa
Tomohisa
T
Tsuda
Hidetaka
H
Obara
Kazuo
K
Nakayama
Koichi
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004396:Coloring Agents / Q000494:pharmacology; D004285:Dogs; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005682:Gadolinium / Q000378:metabolism; D066298:In Vitro Techniques; D007477:Ions / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009529:Nicardipine / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D012430:Ruthenium Red / Q000494:pharmacology; D013314:Stress, Mechanical; D019284:Thapsigargin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D004396:Coloring Agents; D007477:Ions; D014665:Vasodilator Agents; D012430:Ruthenium Red; D009544:Niflumic Acid; D004533:Egtazic Acid; D019284:Thapsigargin; D005682:Gadolinium; D009529:Nicardipine; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium