Role of IP(3) in modulation of spontaneous activity in pacemaker cells of rabbit urethra.

Sergeant, Gerard P. and Hollywood, Mark A. and McCloskey, K. D. and McHale, Noel G. and Thornbury, Keith D. (2001) Role of IP(3) in modulation of spontaneous activity in pacemaker cells of rabbit urethra. Am J Physiol Cell Physiol., 280 (5). pp. 1349-1356.

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Isolated interstitial ("pacemaker") cells from rabbit urethra were examined using the perforated-patch technique. Under voltage clamp at -60 mV, these cells fired large spontaneous transient inward currents (STICs), averaging -860 pA and >1 s in duration, which could account for urethral pacemaker activity. Spontaneous transient outward currents (STOCs) were also observed and fell into two categories, "fast" (<100 ms in duration) and "slow" (>1 s in duration). The latter were coupled to STICs, suggesting that they shared the same mechanism, while the former occurred independently at faster rates. All of these currents were abolished by cyclopiazonic acid, caffeine, or ryanodine, suggesting that they were activated by Ca(2+) release. When D-myo-inositol 1,4,5-trisphosphate (IP(3))-sensitive stores were blocked with 2-aminoethoxydiphenyl borate, the STICs and slow STOCs were abolished, but the fast STOCs remained. In contrast, the fast STOCs were more nifedipine sensitive than the STICs or the slow STOCs. These results suggest that while fast STOCs are mediated by a mechanism similar to STOCs in smooth muscle, STICs and slow STOCs are driven by IP(3). These results support the hypothesis that pacemaker activity in the urethra is driven by the IP(3)-sensitive store.

Item Type: Article
Uncontrolled Keywords: Animals; Boron Compounds/pharmacology; Caffeine/pharmacology; Calcium/physiology; Cell Membrane/drug effects; Cell Membrane/physiology; Female; Indoles/pharmacology; Inositol 1,4,5-Trisphosphate/pharmacology; Inositol 1,4,5-Trisphosphate/physiology; Male; Membrane Potentials/drug effects; Membrane Potentials/physiology; Muscle, Smooth/cytology; Muscle, Smooth/physiology; Nifedipine/pharmacology; Rabbits; Ryanodine/pharmacology; Urethra/cytology; Urethra/physiology; Urinary Bladder/cytology; Urinary Bladder/physiology
Subjects: Science
Research Centres: Smooth Muscle Research Centre
Depositing User: Concepta Woods
Date Deposited: 08 Mar 2012 13:18
Last Modified: 11 Nov 2014 16:10

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