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Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal

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Abstract

Cyclic guanosine 3′,5′-monophosphate (cGMP) inhibited the generation of pacemaker activity in interstitial cells of Cajal (ICCs) from the small intestine. However, cGMP role on pacemaker activity in colonic ICCs has not been reported yet. Thus, we investigated the role of cGMP in pacemaker activity regulation by colonic ICCs. We performed a whole-cell patch-clamp and Ca2+ imaging in cultured ICCs from mouse colon. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) increased the pacemaker potential frequency, whereas zaprinast (an inhibitor of phosphodiesterase) and cell-permeable 8-bromo-cGMP decreased the pacemaker potential frequency. KT-5823 (an inhibitor of protein kinase G [PKG]) did not affect the pacemaker potential. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide [NO] synthase) increased the pacemaker potential frequency, whereas (±)-S-nitroso-N-acetylpenicillamine (SNAP, a NO donor) decreased the pacemaker potential frequency. Glibenclamide (an ATP-sensitive K+ channel blocker) did not block the effects of cell-permeable 8-bromo-cGMP and SNAP. Recordings of spontaneous intracellular Ca2+ ([Ca2+]i) oscillations revealed that ODQ and L-NAME increased [Ca2+]i oscillations. In contrast, zaprinast, 8-bromo cGMP, and SNAP decreased the [Ca2+]i oscillations. Basal cGMP levels regulate the resting pacemaker potential frequency by the alteration on Ca2+ release via a PKG-independent pathway. Additionally, the endogenous release of NO seems to be responsible maintaining basal cGMP levels in colonic ICCs.

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Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education, Science and Technology [2011–0006525].

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The authors disclose no conflicts.

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Authors and Affiliations

  1. Department of Physiology, College of Medicine, Chosun University, 309 Pilmun-daero, Dongku, Gwangju, 501-375, Korea

    Pawan Kumar Shahi, Seok Choi & Jae Yeoul Jun

  2. Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea

    Yu Jin Jeong & Chan Guk Park

  3. Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea

    Insuk So

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  1. Pawan Kumar Shahi
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  2. Seok Choi
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  3. Yu Jin Jeong
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  4. Chan Guk Park
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  5. Insuk So
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  6. Jae Yeoul Jun
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Correspondence to Jae Yeoul Jun.

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Shahi, P.K., Choi, S., Jeong, Y.J. et al. Basal cGMP regulates the resting pacemaker potential frequency of cultured mouse colonic interstitial cells of Cajal. Naunyn-Schmiedeberg's Arch Pharmacol 387, 641–648 (2014). https://doi.org/10.1007/s00210-014-0976-2

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  • DOI: https://doi.org/10.1007/s00210-014-0976-2

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