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T-type Ca(2+) Channel Modulation by Otilonium Bromide

T-type Ca(2+) Channel Modulation by Otilonium Bromide

Peter R Strege, Lei Sha, Arthur Beyder, Cheryl E Bernard, Edward Perez-Reyes, Stefano Evangelista, Simon J Gibbons, Joseph H Szurszewski, Gianrico Farrugia

Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G706-13.

PMID: 20203058

Abstract:

Antispasmodics are used clinically to treat a variety of gastrointestinal disorders by inhibition of smooth muscle contraction. The main pathway for smooth muscle Ca(2+) entry is through L-type channels; however, there is increasing evidence that T-type Ca(2+) channels also play a role in regulating contractility. Otilonium bromide, an antispasmodic, has previously been shown to inhibit L-type Ca(2+) channels and colonic contractile activity. The objective of this study was to determine whether otilonium bromide also inhibits T-type Ca(2+) channels. Whole cell currents were recorded by patch-clamp technique from HEK293 cells transfected with cDNAs encoding the T-type Ca(2+) channels, Ca(V)3.1 (alpha1G), Ca(V)3.2 (alpha1H), or Ca(V)3.3 (alpha1I) alpha subunits. Extracellular solution was exchanged with otilonium bromide (10(-8) to 10(-5) M). Otilonium bromide reversibly blocked all T-type Ca(2+) channels with a significantly greater affinity for Ca(V)3.3 than Ca(V)3.1 or Ca(V)3.2. Additionally, the drug slowed inactivation in Ca(V)3.1 and Ca(V)3.3. Inhibition of T-type Ca(2+) channels may contribute to inhibition of contractility by otilonium bromide. This may represent a new mechanism of action for antispasmodics and may contribute to the observed increased clinical effectiveness of antispasmodics compared with selective L-type Ca(2+) channel blockers.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP134640850	2,3-Dimethylphenylmagnesium bromide		134640-85-0	Price
AP30897860	2,5-Dimethylphenylmagnesium bromide		30897-86-0	Price

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