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

Sergeant, Gerard P. and Thornbury, Keith D. and McHale, Noel G. and Hollywood, Mark A. (2002) Characterization of norepinephrine-evoked inward currents in interstitial cells isolated from the rabbit urethra. Am J Physiol Cell Physiol., 283 (3). pp. 885-894.

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Abstract

Freshly dispersed interstitial cells from the rabbit urethra were studied by using the perforated-patch technique. When cells were voltage clamped at -60 mV and exposed to 10 microM norepinephrine (NE) 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 microM) or prazosin (1 microM), suggesting that the effects of NE were mediated via alpha(1)-adrenoceptors. NE-evoked currents were depressed by the blockers of Ca(2+)-activated Cl(-) currents, niflumic acid (10 microM), and 9-anthracenecarboxylic acid (9-AC, 1 mM). The reversal potential of the above currents changed in a predictable manner when the Cl(-) equilibrium potential was altered, again suggesting that they were due to activation of a Cl(-) conductance. NE-evoked currents were decreased by 10 microM cyclopiazonic acid, suggesting that they were dependent on store-released Ca(2+). Inhibition of NE-evoked currents by the phospholipase C inhibitor 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate (100 microM) suggested that NE releases Ca(2+) via an inositol 1,4,5-trisphosphate (IP(3))-dependent mechanism. These results support the idea that stimulation of alpha(1)-adrenoceptors releases Ca(2+) from an IP(3)-sensitive store, which in turn activates Ca(2+)-activated Cl(-) 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.

Item Type:	Article
Uncontrolled Keywords:	Adrenergic alpha-1 Receptor Antagonists ; Animals ; Anthracenes/pharmacology ; Calcium/metabolism ; Calcium-Transporting ATPases/antagonists & inhibitors ; Cell Separation ; Chloride Channels/antagonists & inhibitors ; Chloride Channels/metabolism ; Enzyme Inhibitors/pharmacology ; Indoles/pharmacology ; Inositol 1,4,5-Trisphosphate/metabolism ; Membrane Potentials/drug effects ; Membrane Potentials/physiology ; Niflumic Acid/pharmacology ; Norepinephrine/pharmacology* ; Patch-Clamp Techniques ; Phentolamine/pharmacology ; Prazosin/pharmacology ; Rabbits ; Receptors, Adrenergic, alpha-1/metabolism ; Type C Phospholipases/antagonists & inhibitors ; Urethra/cytology ; Urethra/drug effects* ; Urethra/metabolism*
Subjects:	Science
Research Centres:	Smooth Muscle Research Centre
Depositing User:	Concepta Woods
Date Deposited:	08 Mar 2012 11:13
Last Modified:	11 Nov 2014 16:10
URI:	https://eprints.dkit.ie/id/eprint/200

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