Low levels of KATP channel activation decrease excitability and contractility of urinary bladder

Georgi Petkov, Thomas J. Heppner, Adrian D. Bonev, Gerald M. Herrera, Mark T. Nelson

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Activation of ATP-sensitive potassium (KATP) channels can regulate smooth muscle function through membrane potential hyperpolarization. A critical issue in understanding the role of KATP channels is the relationship between channel activation and the effect on tissue function. Here, we explored this relationship in urinary bladder smooth muscle (UBSM) from the detrusor by activating KATP channels with the synthetic compounds N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZD-6169) and levcromakalim. The effects of ZD-6169 and levcromakalim on KATP channel currents in isolated UBSM cells, on action potentials, and on related phasic contractions of isolated UBSM strips were examined. ZD-6169 and levcromakalim at 1.02 and 2.63 μM, respectively, caused half-maximal activation (K1/2) of KATP currents in single UBSM cells (see Heppner TJ, Bonev A, Li JH, Kau ST, and Nelson MT. Pharmacology 53: 170-179, 1996). In contrast, much lower concentrations (K1/2 = 47 nM for ZD-6169 and K1/2 = 38 nM for levcromakalim) caused inhibition of action potentials and phasic contractions of UBSM. The results suggest that activation of <1% of KATP channels is sufficient to inhibit significantly action potentials and the related phasic contractions.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume280
Issue number5 49-5
StatePublished - May 1 2001
Externally publishedYes

Fingerprint

KATP Channels
Cromakalim
Urinary Bladder
Smooth Muscle
Action Potentials
Smooth Muscle Myocytes
Membrane Potentials
Pharmacology
Zeneca ZD 6169

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Low levels of KATP channel activation decrease excitability and contractility of urinary bladder. / Petkov, Georgi; Heppner, Thomas J.; Bonev, Adrian D.; Herrera, Gerald M.; Nelson, Mark T.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 280, No. 5 49-5, 01.05.2001.

Research output: Contribution to journalArticle

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