TY - JOUR T1 - AXON REFLEXES EVOKED BY TRPV1 ACTIVATION ARE MEDIATED BY TTX-RESISTANT VOLTAGE GATED Na<sup>+</sup> CHANNELS IN INTESTINAL AFFERENT NERVES JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.110.165969 SP - jpet.110.165969 AU - Marcela Miranda-Morales AU - Fernando Ochoa-Cortes AU - Emily Stern AU - Alan E Lomax AU - Stephen Vanner Y1 - 2010/01/01 UR - http://jpet.aspetjournals.org/content/early/2010/05/03/jpet.110.165969.abstract N2 - Capsaicin-sensitive nerves mediate axon vasodilator reflexes in the intestine but the ion channels underlying action potential (AP) propagation are poorly understood. To examine the role of voltage gated Na+ channels underlying these reflexes, we measured vasomotor and electrophysiological responses elicited by capsaicin in guinea pig and mouse dorsal root ganglia neurons, submucosal arterioles and mesenteric arteries in vitro. TRPV1 agonists dilated guinea pig ileal submucosal arterioles and were blocked by capsazepine and ruthenium red. In double chamber baths, capsaicin-evoked activation of TRPV1 on proximal perivascular nerves in the left chamber evoked dilations of the distal segment of the submucosal arteriole in the right chamber. Dilations were TTX (1 μM) resistant but reducing extracellular Na+ (10% solution) or applying the Nav 1.8 antagonist A-803467 (1 μM) in the proximal chamber blocked capsaicin-evoked dilations in the distal chamber (88%; P = 0.01 and 75%, P&lt;0.02 respectively). In mouse mesenteric arteries, electrical field stimulation and capsaicin (2 μM) evoked dilations which were also TTX-resistant. In perforated patch clamp recordings, action potentials in mouse and guinea pig capsaicin-sensitive DRG neurons were TTX-resistant but blocked by 10% extracellular Na+. When capsaicin-evoked AP conduction was studied in in vitro ileal multi-unit afferent nerve preparations, capsaicin responses were elicited in the presence of TTX whereas distention-evoked responses were almost completely blocked by TTX. Together, these data provide evidence for TTX-resistant AP conduction in extrinsic sensory neurons that innervate guinea pig and mouse intestine, and suggest this neural propagation is sufficient to mediate axon reflexes in the intestine.The American Society for Pharmacology and Experimental Therapeutics ER -