RESUMEN
Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (40 percent) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia.
Asunto(s)
Animales , Ratas , Ácido Láctico/metabolismo , Canales de Sodio/fisiología , Dolor/fisiopatología , Isquemia/fisiopatología , Neuronas Aferentes/fisiología , Proteínas de la Membrana/fisiología , Proteínas del Tejido Nervioso/fisiología , Concentración de Iones de HidrógenoRESUMEN
The influence of 6-hydroxydopamine (6-OHDA) pretreatment on zylazine (XLZ)-induced antinociception was studied in mice using the writhing test (60 mg/Kg acetic acid, ip, as the algogenic compound administered 10 min after 0.5 0.75 mg/Kg XLZ, sc). 6-OHDA (100 mgKg-1 injection-1 administered ip on days 1, 3, 5, 7, 9 and 11 after bith) did not modify XLZ- induced antinociception, suggesting that effects is mediated by postsynaptic alpha-2 adrnoceptors