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Phentolamine inhibits the pacemaker activity of mouse interstitial cells of Cajal by activating ATP-sensitive K+ channels

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Abstract

The aim of this study was to clarify if phentolamine has proven effects on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine involving the ATPsensitive K+ channels and adrenergic receptor. The actions of phentolamine on pacemaker activities were investigated using whole-cell patch-clamp technique and intracellular Ca2+ analysis at 30°C in cultured mouse intestinal ICC. ICC generated spontaneous pacemaker currents at a holding potential of −70 mV. Treatment with phentolamine reduced the frequency and amplitude of the pacemaker currents and increased the resting outward currents. Moreover, under current clamping (I = 0), phentolamine hyperpolarized the ICC membrane and decreased the amplitude of the pacemaker potentials. We also observed that phentolamine inhibited spontaneous [Ca2+]i oscillations in ICC. The alpha-adrenergic drugs prazosin, yohimbine, methoxamine, and clonidine had no effect on ICC intestinal pacemaker activity and did not block phentolamine-induced effects. Phentolamine-induced effects on the pacemaker currents and the pacemaker potentials were significantly inhibited by ATP sensitive K+ channel blocker glibenclamide, but not by TEA, apamin, or 4-aminopyridine. In addition, the NO synthase inhibitor, L-NAME and the guanylate cyclase inhibitor, ODQ were incapable of blocking the phentolamine-induced effects. These results demonstrate that phentolamine regulates the pacemaker activity of ICC via ATP-sensitive K+ channel activation. Phentolamine could act through an adrenergic receptor- and also through NO-independent mechanism that involves intracellular Ca2+ signaling.

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Authors and Affiliations

  1. Department of Neurology, College of Medicine, Chosun University, Gwangju, 501-759, Korea

    Seung Whan Ahn & Jin Ho Kim

  2. Department of Anesthesiology, College of Medicine, Chosun University, Gwangju, 501-759, Korea

    Sang Hun Kim

  3. Department of Physiology, College of Medicine, Chosun University, Gwangju, 501-759, Korea

    Seok Choi, Cheol Ho Yeum, Hee Wook Wie, Jae Myeong Sun & Jae Yeoul Jun

  4. Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, 110-799, Korea

    Insuk So

  5. Department of Physiology, College of Medicine, Chosun University, 375 Seosuk-dong, Gwangju, 501-759, Korea

    Jae Yeoul Jun

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  1. Seung Whan Ahn
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  2. Sang Hun Kim
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  3. Jin Ho Kim
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Correspondence to Jae Yeoul Jun.

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Ahn, S.W., Kim, S.H., Kim, J.H. et al. Phentolamine inhibits the pacemaker activity of mouse interstitial cells of Cajal by activating ATP-sensitive K+ channels. Arch. Pharm. Res. 33, 479–489 (2010). https://doi.org/10.1007/s12272-010-0319-x

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  • DOI: https://doi.org/10.1007/s12272-010-0319-x

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