Ca2+-dependence and nifedipine-sensitivity of vascular tone and contractility in the isolated superfused spiral modiolar artery in vitro.
The regulation of the vascular diameter of the spiral modiolar artery may play a major role in the regulation of cochlear blood flow and tissue oxygenation since the spiral modiolar artery provides the main blood supply to the cochlea. The goal of the present study was to determine whether vascular tone and contractility of the spiral modiolar artery depend on the presence of extracellular Ca2+ and involves nifedipine-sensitive Ca2+ channels. The spiral modiolar artery was isolated and superfused in vitro and the diameter was measured continuously by video microscopy. Isolated segments of the spiral modiolar artery had an outer diameter of 61 +/- 3 microm (n = 59) and displayed vasomotion characterized by 5-15 clearly distinguishable constrictions per min. Removal of Ca2+ from the superfusion medium caused a reversible relaxation and cessation of vasomotion and was used to determine the magnitude of basal vascular tone. The basal vascular tone consisted of a sustained reduction of the vascular diameter to 95.1 +/- 0.3% (n = 51) of the maximal diameter in Ca2+-free medium. Nifedipine reduced the basal vascular tone with an IC50 of (1.1 +/- 0.3) x 10(-9)) M although 22% of the basal vascular tone was insensitive to nifedipine. Elevation of the K+ concentration from 3.6 to 150 mM caused a transient vasoconstriction which was dependent on the presence of extracellular Ca2+. Nifedipine fully inhibited K+-induced vasoconstriction with an IC50 of (2.0 +/- 0.7) x 10(-9) M. Norepinephrine (10(-4) M) caused a transient vasoconstriction and an increase of vasomotion at branch points of the spiral modiolar artery. Norepinephrine-induced vasoconstriction was fully inhibited in the absence of Ca2+ and partially inhibited by 10(-7) M nifedipine. These observations suggest that the spiral modiolar artery contains voltage-dependent nifedipine-sensitive Ca2+ channels which are involved in the maintenance of basal vascular tone as well as in the mediation of K+- and norepinephrine-induced contractility. Further, the data suggest that cytosolic Ca2+ stores, if present in the spiral modiolar artery, are of limited capacity compared to other vessels.
Wangemann
P
P
Cell Physiology Laboratory, Boys Town National Research Hospital, Omaha, NE 68131, USA. Wange@Boystown.org
Cohn
E S
ES
Gruber
D D
DD
Gratton
M A
MA
D000818:Animals; D001158:Arteries / Q000033:anatomy & histology / Q000187:drug effects; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects*; D005849:Gerbillinae; D066298:In Vitro Techniques; D018715:Microscopy, Video; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium; D012039:Regional Blood Flow / Q000187:drug effects; D012984:Software; D013223:Statistics as Topic; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D009543:Nifedipine; D011188:Potassium; D002118:Calcium