RT Journal Article
T1 Involvement of cyclic nucleotide-gated channels in spontaneous activity generated in isolated interstitial cells of Cajal from the rabbit urethra.
A1 Sancho González, María
A1 Bradley, Eamonn
A1 García Pascual, María De Los Ángeles
A1 Triguero Robles, Domingo
A1 Thornbury, Keith D.
A1 Hollywood, Mark A.
A1 Sergeant, Gerard P.
AB Cyclic nucleotide-gated (CNG) channels are non-selective cation channels that mediate influx of extracellular Na and Ca in various cell types. L-cis-Diltiazem, a CNG channel blocker, inhibits contraction of urethral smooth muscle (USM), however the mechanisms underlying this effect are still unclear. We investigated the possibility that CNG channels contribute to spontaneous pacemaker activity in freshly isolated interstitial cells of Cajal (ICC) isolated from the rabbit urethra (RUICC). Using immunocytochemistry, we found intense CNG1-immunoreactivity in vimentin-immunoreactive RUICC, mainly within patches of the cellular body and processes. In contrast, α-actin immunoreactive smooth muscle cells (SMC) did not show significant reactivity to a specific CNGA1 antibody. Freshly isolated RUICC, voltage clamped at -60mV, developed spontaneous transient inward currents (STICs) that were inhibited by L-cis-Diltiazem (50µM). Similarly, L-cis-Diltiazem (50µM) also inhibited Ca waves in isolated RUICC, recorded using a Nipkow spinning disk confocal microscope. L-cis-Diltiazem (50µM) did not affect caffeine (10mM)-induced Ca transients, but significantly reduced phenylephrine-evoked Ca oscillations and inward currents in in RUICC. L-type Ca current amplitude in isolated SMC was reduced by ~18% in the presence of L-cis-Diltiazem (50µM), however D-cis-Diltiazem, a recognised L-type Ca channel blocker, abolished L-type Ca current but did not affect Ca waves or STICs in RUICC. These results indicate that the effects of L-cis-diltiazem on rabbit USM could be mediated by inhibition of CNG1 channels that are present in urethral ICC and therefore CNG channels contribute to spontaneous activity in these cells.
PB Elsevier
YR 2017
FD 2017-11-05
LK https://hdl.handle.net/20.500.14352/120877
UL https://hdl.handle.net/20.500.14352/120877
LA eng
NO Sancho M, Bradley E, Garcia-Pascual A, Triguero D, Thornbury KD, Hollywood MA, Sergeant GP. Involvement of cyclic nucleotide-gated channels in spontaneous activity generated in isolated interstitial cells of Cajal from the rabbit urethra. Eur J Pharmacol. 2017 Nov 5;814:216-225.
NO Enterprise Ireland
NO Ministerio de Economia y Competitividad
DS Docta Complutense
RD 17 mar 2026