title: IP3 decreases coronary artery tone via activating the BKCa channel of coronary artery smooth muscle cells in pigs.
abstract: Large conductance Ca(2+)-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 Ca(2+) 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 Ca(2+) sensitivity of the channels.
authors.affiliation: Key Laboratory of Medical Electrophysiology, Ministry of Education, The Institute of Cardiovascular Research, Luzhou Medical College, Luzhou 646000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Peng-Yun
authors.initials: PY
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Fang
authors.initials: F
authors.lastname: Cai
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Tan
authors.forename: Miao-Ling
authors.initials: ML
authors.lastname: Li
authors.forename: Zhi-Fei
authors.initials: ZF
authors.lastname: Liu
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Zeng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D013552:Swine / Q000523:psychology*; D014664:Vasodilation
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015544:Inositol 1,4,5-Trisphosphate
keywords: Coronary artery; Inositol trisphosphate (IP3); Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel; Vascular smooth muscle