Type

Journal Article

Authors

Keith D. Thornbury
Noel G McHale
Mark A Hollywood
Gerard P Sergeant
M. Craven

Subjects

Pharmacology

Topics
smooth muscle cells carboxylic acid science nitric oxide sarcoplasmic reticulum niflumic acid modulation whole cell patch clamp technique

Modulation of spontaneous Ca2+-activated Cl- currents in the rabbit corpus cavernosum by the nitric oxide-cGMP pathway. (2004)

Abstract The whole-cell perforated patch clamp technique was used to study membrane currents in isolated rabbit corpus cavernosum smooth muscle cells. Depolarization from -80 mV to the range -40 to -10 mV evoked a nifedipine-sensitive Ca(2+) current that was followed by a slower inward current that activated over several hundred milliseconds. The slow current reversed near the Cl(-) equilibrium potential (E(Cl)) and was reduced by anthracene-9-carboxylic acid (A9C; 1 mm) and niflumic acid (100 microm), suggesting that it was a Ca(2+)-activated Cl(-) current. When held constantly at -60 mV, over 70% of cells fired spontaneous transient inward currents (STICs), the amplitudes of which were reduced by A9C and niflumic acid. STICs reversed near E(Cl) in a symmetrical Cl(-) gradient and when [Cl(-)](o) was substituted with glutamate or I(-), the reversal potential shifted to more positive or more negative values, respectively, confirming that STICs were mediated by Cl(-) channels. STICS were also blocked by cyclopiazonic acid, 2-aminoethoxydiphenyl borate (2-APB) and 2-nitro-4-carboxyl-N,N-diphenylcarbamate (NCDC), suggesting that they depended on IP(3)-mediated Ca(2+)-release from the sarcoplasmic reticulum. Modulation by the NO-cGMP pathway was investigated by applying nitrosocysteine, 3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole (YC-1), and 8-bromo cGMP, all three of which abolished STIC activity. YC-1 also reduced noradrenaline-evoked inward currents, but had no effect on similar currents evoked by caffeine, suggesting that cGMP selectively inhibited IP(3)-mediated Ca(2+) release. We propose that Ca(2+)-activated Cl(-) currents underlie detumescent tone in the corpus cavernosum, and that modulation of this mechanism by the NO-cGMP pathway is important during penile erection.
Collections Ireland -> Dundalk IT -> Subject = Science
Ireland -> Dundalk IT -> Open Access DRIVERset
Ireland -> Dundalk IT -> Status = Published
Ireland -> Dundalk IT -> Type = Article

Full list of authors on original publication

Keith D. Thornbury, Noel G McHale, Mark A Hollywood, Gerard P Sergeant, M. Craven

Experts in our system

1
Keith D. Thornbury
Dundalk IT
Total Publications: 27
 
2
Noel G McHale
Dundalk IT
Total Publications: 35
 
3
Mark A Hollywood
Dundalk IT
Total Publications: 35
 
4
Gerard P Sergeant
Dundalk IT
Total Publications: 24