Ryanodine-induced vasoconstriction of the gerbil spiral modiolar artery depends on the Ca2+ sensitivity but not on Ca2+ sparks or BK channels

Abstract

BackgroundIn many vascular smooth muscle cells (SMCs), ryanodine receptor-mediated Ca2+ sparks activate large-conductance Ca2+-activated K+ (BK) channels leading to lowered SMC [Ca2+]i and vasodilation. Here we investigated whether Ca2+ sparks regulate SMC global [Ca2+]i and diameter in the spiral modiolar artery (SMA) by activating BK channels.MethodsSMAs were isolated from adult female gerbils, loaded with the Ca2+-sensitive flourescent dye fluo-4 and pressurized using a concentric double-pipette system. Ca2+ signals and vascular diameter changes were recorded using a laser-scanning confocal imaging system. Effects of various pharmacological agents on Ca2+ signals and vascular diameter were analyzed.ResultsCa2+ sparks and waves were observed in pressurized SMAs. Inhibition of Ca2+ sparks with ryanodine increased global Ca2+ and constricted SMA at 40 cmH2O but inhibition of Ca2+ sparks with tetracaine or inhibition of BK channels with iberiotoxin at 40 cmH2O did not produce a similar effect. The ryanodine-induced vasoconstriction observed at 40 cmH2O was abolished at 60 cmH2O, consistent with a greater Ca2+-sensitivity of constriction at 40 cmH2O than at 60 cmH2O. When the Ca2+-sensitivity of the SMA was increased by prior application of 1 nM endothelin-1, ryanodine induced a robust vasoconstriction at 60 cmH2O.ConclusionsThe results suggest that Ca2+ sparks, while present, do not regulate vascular diameter in the SMA by activating BK channels and that the regulation of vascular diameter in the SMA is determined by the Ca2+-sensitivity of constriction.

Protective Effects of Adiponectin against Cobalt Chloride-Induced Apoptosis of Smooth Muscle Cells via cAMP/PKA Pathway

“…Furthermore, regulation of cochlear blood flow is essential for hearing and is important as a treatment strategy for the restoration of hearing loss in humans [ 1 , 2 ]. In addition, due to the high energy consumption of auditory conduction, the blood supply of the spiral modiolar artery (SMA) is considered essential for maintaining the function of the hearing device [ 3 ]. And studies on the inner ear circulatory system have confirmed that, on the one hand, the cochlear strong ability of blood flow autonomous regulation could ensure the blood supply of local tissues, and on the other hand, this ability could reduce the impact of the rapid changes of blood pressure and also maintain water and electrolyte balance in the local tissues of the cochlea [ 4 ].…”

Primary Cultivation and Identification of Vascular Smooth Muscle Cells from the Spiral Modiolar Artery of Guinea Pigs

“…Numerous studies have shown that disorders in the circulatory system in the inner ear are closely linked to sudden deafness [1,2], Meniere’s disease [3], senile hearing loss [4], and ototoxicity-induced hearing loss [5]. Moreover, the blood supply of the spiral modiolar artery (SMA) is believed to play a vital role in maintaining the function of the auditory apparatus because of the high energy consumption of auditory conduction process [6–8].…”

“…Hence, if abnormal changes occur in the SMA, such as vasospasm, this change would reduce or even completely interrupt the cochlear blood supply. This condition contributes to blood circulation disorders in the inner ear and cochlear dysfunction, such as dizziness, tinnitus, and other symptoms [8,10]. Hence, the blood supply of SMA may have a decisive impact on maintaining normal hearing [11].…”