IP3 decreases coronary artery tone via activating the BKCa channel of coronary artery smooth muscle cells in pigs

• Published in: Biochemical and biophysical research communications 2013-09, Vol.439 (3), p.363-368
• Main Authors: Yang, Yan, Li, Peng-Yun, Cheng, Jun, Cai, Fang, Lei, Ming, Tan, Xiao-Qiu, Li, Miao-Ling, Liu, Zhi-Fei, Zeng, Xiao-Rong
• Format: Article
• Language: English
• Subjects: Animals; Cells, Cultured; Coronary artery; Coronary Vessels - physiology; Inositol 1,4,5-Trisphosphate - metabolism; Inositol 1,4,5-Trisphosphate Receptors - metabolism; Inositol trisphosphate (IP3); Large-conductance Ca2+-activated K+ (BKCa) channel; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - physiology; Swine - psychology; Vascular smooth muscle; Vasodilation
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.08.079

•IP3 activates BKCa channels and exerts a coronary artery-relaxing effect.•IP3 enhances the STOC via IP3 receptor.•IP3 stimulates the Macro-current by increasing the Ca2+ sensitivity of channels. Large conductance Ca2+-activated K+ channel (BKCa) is a potential target for coronary artery-relaxing medication, but its functional regulation is largely unknown. Here, we report that inositol trisphosphate (IP3) activated BKCa channels in isolated porcine coronary artery smooth muscle cells and by which decreased the coronary artery tone. Both endogenous and exogenous IP3 increased the spontaneous transient outward K+ currents (STOC, a component pattern of BKCa currents) in perforated and regular whole-cell recordings, which was dependent on the activity of IP3 receptors. IP3 also increased the macroscopic currents (MC, another component pattern of BKCa currents) via an IP3 receptor- and sarcoplasmic Ca2+ mobilization-independent pathway. In inside-out patch recordings, direct application of IP3 to the cytosolic side increased the open probability of single BKCa channel in an IP3 receptor-independent manner. We conclude that IP3 is an activator of BKCa channels in porcine coronary smooth muscle cells and exerts a coronary artery-relaxing effect. The activation of BKCa channels by IP3 involves the enhancement of STOCs via IP3 receptors and stimulation of MC by increasing the Ca2+ sensitivity of the channels.