TY - JOUR T1 - Peptidyl Inhibitors of <em>Shaker</em>-Type K<sub>v</sub>1 Channels Elicit Twitches in Guinea Pig Ileum by Blocking K<sub>v</sub>1.1 at Enteric Nervous System and Enhancing Acetylcholine Release JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1517 LP - 1522 VL - 289 IS - 3 AU - Guilherme Suarez-Kurtz AU - Rosane Vianna-Jorge AU - Bianca F. Pereira AU - Maria Luisa Garcia AU - Gregory J. Kaczorowski Y1 - 1999/06/01 UR - http://jpet.aspetjournals.org/content/289/3/1517.abstract N2 - Potent and selective peptidyl blockers of theShaker-type (Kv1) voltage-gated potassium channels were used to determine the role of these channels in regulating the spontaneous motility of smooth muscle preparations. Margatoxin (MgTX), kaliotoxin, and agitoxin-2 at 1 to 10 nM and agitoxin-1 at 50 to 100 nM induce twitches in guinea pig ileum strips. These twitches are abolished by tetrodotoxin (TTX, 0.5 μM), atropine (1 μM), hexamethonium (10 μM), or nifedipine (0.1 μM). It is proposed that blockade of Kv1 channels by MgTX, kaliotoxin, or the agitoxins increases excitability of intramural nerve plexuses in the ileum, promoting release of acetylcholine from excitatory motor nerve terminals. This, in turn, leads to Ca2+-dependent action potentials and twitching of the muscle fibers. MgTX does not induce twitches in several other guinea pig and/or rat vascular, genitourinary, or gastrointestinal smooth muscles, although small increases in spontaneous myogenic activity may be seen in detrusor muscle exposed to &gt;30 nM MgTX. This effect is not reversed by TTX or atropine. The TTX- and atropine-sensitive twitches of guinea pig ileum are also induced by nanomolar concentrations of α-dendrotoxin, a selective blocker of Shaker Kv1.1 and 1.2 subtypes, or stichodactylatoxin, a peptide isolated from sea anemone that displays high affinity for Kv1.1 and 1.3, but not by charybdotoxin, which blocks Kv1.2 and 1.3 but not 1.1. The data taken together suggest that high-affinity blockade of Kv1.1 underlies the ability of MgTX, kaliotoxin, agitoxin-1, agitoxin-2, α-dendrotoxin, and stichodactylatoxin to elicit TTX-sensitive twitches in guinea pig ileum. The American Society for Pharmacology and Experimental Therapeutics ER -