Inhibition of Cholinergic Neurotransmission in Guinea Pig Trachea by NS1619, a Putative Activator of Large-Conductance, Calcium-Activated Potassium Channels,

摘要: Indirect functional studies suggest that large-conductance calcium-activated potassium channels (BKCa channels) are involved in the control of ACh release from postganglionic, parasympathetic nerve terminals airways. The role BKCa regulating cholinergic neurotransmission was assessed by 1) investigating effect putative channel opener NS1619 on contractile responses and output evoked electrical field stimulation (EFS: 40 V, 0.5 ms, 4 Hz for 15 s every min) comparing obtained with inhibition EFS-evoked oxotremorine M, a muscarinic agonist, 2) evaluating sensitivity these to blocker iberiotoxin (IbTX). (30 μM) inhibited 60.0%. In contrast, had no exogenous (1 μM), which indicated it acting prejunctionally. significantly EFS-induced 33.9%. Oxotremorine M suppressed concentration-dependent manner (at 1 μM, 77.4% inhibition). neither case reversed IbTX (100 nM). Collectively, mechanical data inhibits interacting failure reverse inhibitory action indicates activation autoinhibitory receptors is not coupled opening IbTX-sensitive channels. Therefore, we propose caution be exercised when using as an activator