Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol (May 15, 2002). doi:10.1152/ajpcell.00085.2002
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Articles in PresS, published online ahead of print May 15, 2002
Am J Physiol Cell Physiol, 10.1152/ajpcell.00085.2002
Submitted on February 25, 2002
Accepted on May 3, 2002

Characterization of noradrenaline-evoked inward currents in interstitial cells isolated from the rabbit urethra

Gerard P. Sergeant1, Keith D. Thornbury1, Noel G. McHale1, and Mark A. Hollywood1*

1 Smooth Muscle Group, Physiology Department, Queen's University of Belfast, Belfast, Co Antrim, Ireland

* To whom correspondence should be addressed. E-mail: m.hollywood{at}qub.ac.uk.

Freshly dispersed interstitial cells from the rabbit urethra were studied using the perforated-patch technique. When cells were voltage clamped at -60 mV and exposed to 10 µM noradrenaline (NA) at 80 s intervals, either large single inward currents or a series of oscillatory inward currents of diminishing amplitude were evoked. These currents were blocked by either phentolamine (1 µM) or prazosin (1 µM), suggesting that the effects of NA were mediated via {alpha}1-adrenoceptors. NA evoked currents were depressed by the blockers of Ca2+-activated chloride currents, niflumic acid (10 µM) and anthracene 9 carboxylic acid (A-9-C, 1 mM). The reversal potential of the above currents changed in a predictable manner when ECl was altered, again suggesting that they were due to activation of a chloride conductance. NA evoked currents were decreased by 10 µM CPA, suggesting that they were dependent on store released calcium. Inhibition of NA evoked currents by the phospholipase C inhibitor 2-nitro-4-carboxyphenyl-n, n-diphenylcarbamate (NCDC, 100 µM) suggested that NA releases calcium from IP3 sensitive stores. These results support the idea that stimulation of {alpha}1-adrenoceptors releases calcium from an IP3-sensitive store, which in turn activates Ca2+-activated chloride current in freshly dispersed interstitial cells of the rabbit urethra. This elevates slow wave frequency in these cells and may underlie the mechanism responsible for increased urethral tone during nerve stimulation.




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