Background: In many vascular smooth muscle cells (SMCs), ryanodine receptor-mediated Ca sparks activate large-conductance Ca-activated K (BK) channels leading to lowered SMC [Ca] and vasodilation. Here we investigated whether Ca sparks regulate SMC global [Ca] and diameter in the spiral modiolar artery (SMA) by activating BK channels.
Methods: SMAs were isolated from adult female gerbils, loaded with the Ca-sensitive flourescent dye fluo-4 and pressurized using a concentric double-pipette system. Ca signals and vascular diameter changes were recorded using a laser-scanning confocal imaging system. Effects of various pharmacological agents on Ca signals and vascular diameter were analyzed.
Results: Ca sparks and waves were observed in pressurized SMAs. Inhibition of Ca sparks with ryanodine increased global Ca and constricted SMA at 40 cmHO but inhibition of Ca sparks with tetracaine or inhibition of BK channels with iberiotoxin at 40 cmHO did not produce a similar effect. The ryanodine-induced vasoconstriction observed at 40 cmHO was abolished at 60 cmHO, consistent with a greater Ca-sensitivity of constriction at 40 cmHO than at 60 cmHO. When the Ca-sensitivity of the SMA was increased by prior application of 1 nM endothelin-1, ryanodine induced a robust vasoconstriction at 60 cmHO.
Conclusions: The results suggest that Ca 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 Ca-sensitivity of constriction.
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| http://dx.doi.org/10.1186/s12899-016-0026-z | DOI Listing |
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