Abstract
Antispasmodics are used clinically to treat a variety of gastrointestinal disorders by inhibition of smooth muscle contraction. The main pathway for smooth muscle Ca2+ entry is through L-type channels; however, there is increasing evidence that T-type Ca+ channels also play a role in regulating contractility. Otilonium bromide, an antispasmodic, has previously been shown to inhibit L-type Ca2+ channels and colonic contractile activity. The objective of this study was to determine whether otilonium bromide also inhibits T-type Ca2+ channels. Whole cell currents were recorded by patch-clamp technique from HEK293 cells transfected with cDNAs encoding the T-type Ca2+ channels, CaV3.1 (α1G), CaV3.2 (α1H), or CaV3.3 (α1I) alpha subunits. Extracellular solution was exchanged with otilonium bromide (10-8 to 10-5 M). Otilonium bromide reversibly blocked all T-type Ca2+ channels with a significantly greater affinity for CaV3.3 than CaV3.1 or CaV3.2. Additionally, the drug slowed inactivation in Ca V3.1 and CaV3.3. Inhibition of T-type Ca2+ 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 Ca2+ channel blockers.
Original language | English (US) |
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Pages (from-to) | G706-G713 |
Journal | American Journal of Physiology - Gastrointestinal and Liver Physiology |
Volume | 298 |
Issue number | 5 |
DOIs | |
State | Published - May 2010 |
Keywords
- Ammonium
- Antispasmodic
- Intestine
- Smooth muscle
- Voltage dependence
ASJC Scopus subject areas
- Physiology
- Hepatology
- Gastroenterology
- Physiology (medical)