Distinct Effects of Ca Sparks on Cerebral Artery and Airway Smooth Muscle Cell Tone in Mice and Humans.

The effects of Ca sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone, as well as the underlying mechanisms, are not clear. In this investigation, we elucidated the underlying mechanisms of the distinct effects of Ca sparks on cerebral artery smooth muscle cells (CASMCs) and airway smooth muscle cells (ASMCs) tone. In CASMCs, owing to the functional loss of Ca-activated Cl (Clca) channels, Ca sparks activated large-conductance Ca-activated K channels (BKs), resulting in a decreases in tone against a spontaneous depolarization-caused high tone in the resting state. In ASMCs, Ca sparks induced relaxation through BKs and contraction via Clca channels. However, the integrated result was contraction because Ca sparks activated BKs prior to Clca channels and Clca channels-induced depolarization was larger than BKs-caused hyperpolarization. However, the effects of Ca sparks on both cell types were determined by L-type voltage-dependent Ca channels (LVDCCs). In addition, compared with ASMCs, CASMCs had great and higher amplitude Ca sparks, a higher density of BKs, and higher Ca and voltage sensitivity of BKs. These differences enhanced the ability of Ca sparks to decrease CASMC and to increase ASMC tone. The higher Ca and voltage sensitivity of BKs in CASMCs than ASMCs were determined by the β1 subunits. Moreover, Ca sparks showed the similar effects on human CASMC and ASMC tone. In conclusions, Ca sparks decrease CASMC tone and increase ASMC tone, mediated by BKs and Clca channels, respectively, and finally determined by LVDCCs.