Activation of the cGMP/PKG pathway inhibits electrical activity in rabbit urethral interstitial cells of Cajal by reducing the spatial spread of Ca2+ waves.

The Journal of Physiology
G P SergeantM A Hollywood

Abstract

In the present study we used a combination of patch clamping and fast confocal Ca2+ imaging to examine the effects of activators of the nitric oxide (NO)/cGMP pathway on pacemaker activity in freshly dispersed ICC from the rabbit urethra, using the amphotericin B perforated patch configuration of the patch-clamp technique. The nitric oxide donor, DEA-NO, the soluble guanylyl cyclase activator YC-1 and the membrane-permeant analogue of cGMP, 8-Br-cGMP inhibited spontaneous transient depolarizations (STDs) and spontaneous transient inward currents (STICs) recorded under current-clamp and voltage-clamp conditions, respectively. Caffeine-evoked Cl- currents were unaltered in the presence of SP-8-Br-PET-cGMPs, suggesting that activation of the cGMP/PKG pathway does not block Cl- channels directly or interfere with Ca2+ release via ryanodine receptors (RyR). However, noradrenaline-evoked Cl- currents were attenuated by SP-8-Br-PET-cGMPs, suggesting that activation of cGMP-dependent protein kinase (PKG) may modulate release of Ca2+ via IP3 receptors (IP3R). When urethral interstitial cells (ICC) were loaded with Fluo4-AM (2 microm), and viewed with a confocal microscope, they fired regular propagating Ca2+ waves, which originated in o...Continue Reading

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Citations

Aug 25, 2007·International Journal of Impotence Research·A F BradingH Hashitani
Jan 11, 2008·American Journal of Physiology. Renal Physiology·Qingli ZhangThomas L Pallone
Sep 21, 2013·Life Sciences·Antonio Celso S Ramos-FilhoEdson Antunes
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Jan 21, 2011·American Journal of Physiology. Renal Physiology·Maria SanchoAngeles Garcia-Pascual
Dec 8, 2019·The Journal of Physiology·Bernard T DrummKenton M Sanders
Sep 13, 2008·The Journal of Physiology·Michael J Berridge
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Jun 18, 2010·Progress in Biophysics and Molecular Biology·Miyako TakakiShinsuke Nakayama
Oct 5, 2010·Cell Calcium·Lionel F Jaffe

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