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Tachyphylaxis to the inhibitory effect of L-type channel blockers on ACh-induced [Ca2+]i oscillations in porcine tracheal myocytes

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Journal of Biomedical Science

Summary

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.

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  1. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS, 39216-4505, USA

    Wen-Shuo Chung & Jerry M. Farley

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Chung, WS., Farley, J.M. Tachyphylaxis to the inhibitory effect of L-type channel blockers on ACh-induced [Ca2+]i oscillations in porcine tracheal myocytes. J Biomed Sci 14, 129–143 (2007). https://doi.org/10.1007/s11373-006-9122-6

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