Ryanodine receptors decant internal Ca store in human and bovine airway smooth muscle

Several putative roles for ryanodine receptors (RyR) were investigated in human and bovine airway smooth muscle. Changes in intracellular Ca concentration ([Ca]i) and membrane current were investigated in single cells by confocal fluorimetry and patch-clamp electrophysiology, respectively, whereas mechanical activity was monitored in intact strips with force transducers. RyR released Ca from the sarcoplasmic reticulum in a ryanodineand chloroethyl phenol (CEP)-sensitive fashion. Neither ryanodine nor CEP inhibited responses to KCl, cholinergic agonists or serotonin, indicating no direct role for RyR in contraction; in fact, there was some augmentation of these responses. In tissues pre-contracted with carbachol, the concentration– response relationships for isoproterenol and salmeterol were unaffected by ryanodine; relaxations due to a nitric oxide donor were also largely unaffected. Finally, it was examined whether RyR were involved in regulating [Ca]i within the subplasmalemmal space using patchclamp electrophysiology as well as Ca fluorimetry: isoproterenol increased [Ca]iand Ca dependent K current activity in a ryanodine-sensitive fashion. In conclusion, ryanodine receptors in airway smooth muscle are not important in directly mediating contraction or relaxation. The current authors speculate instead that these allow the sarcoplasmic reticulum to release Ca towards the plasmalemma (to unload an overly full Ca store and/or increase the Ca-buffering capacity of the sarcoplasmic reticulum) without affecting