- 作者: Wen-Shuo Chung; Jerry M. Farley
- 作者服務機構: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS, 39216-4505, USA
- 中文摘要: --
- 英文摘要: Discrepancies about the role of L-type voltage-gated calcium channels (VGCC) in acetylcholine (ACh)-induced [Ca2+]i oscillations in tracheal smooth muscle cells (TSMCs) have been seen in recent reports. We demonstrate here that ACh-induced [Ca2+]i oscillations in TMCS were reversibly inhibited by three VGCC blockers, nicardipine, nifedipine and verapamil. Prolonged (several minutes) application of VGCC blockers, led to tachyphylaxis; that is, [Ca2+]i oscillations resumed, but at a lower frequency. Brief (15-30 s) removal of VGCC blockers re-sensitized [Ca2+]i oscillations to inhibition by the agents. Calcium oscillations tolerant to VGCC blockers were abolished by KB-R7943, an inhibitor of the reverse mode of Na+ /Ca2+ exchanger (NCX). KB-R7943 alone also abolished ACh-induced [Ca2+]i oscillations. Enhancement of the reverse mode of NCX via removing extracellular Na+ reversed inhibition of ACh-induced [Ca2+]i oscillations by VGCC blockers. Inhibition of non-selective cation channels using Gd3+ slightly reduced the frequency of ACh-induced [Ca2+]i oscillations, but did not prevent the occurrence of tachyphylaxis. Altogether, these results suggest that VGCC and the reverse mode of NCX are two primary Ca2+ entry pathways for maintaining ACh-induced [Ca2+]i oscillations in TSMCs. The two pathways complement each other, and may account for tachyphylaxis of ACh-induced [Ca2+]i oscillations to VGCC blockers.
- 中文關鍵字: --
- 英文關鍵字: calcium oscillations, L-type, NCX, smooth muscle, trachea