ABSTRACT
Dorsal root ganglia (DRG) neurons transduce and convey somatosensory information from the periphery to the central nervous system. Adrenergic mediators are known to modulate nociceptive inputs in DRG neurons, acting as up- or down-regulators of neuronal excitability. They are also important in the development of sympathetic neuropathy. ATP-activated P2X channels and capsaicin-activated TRPV1 channels are directly involved in the transduction of nociceptive stimuli. In this work, we show that long-term (up to 3 days) in vitro stimulation of DRG neurons with selective α1-adrenergic agonist increased slow but not fast ATP-activated currents, with no effect on capsaicin currents. Selective agonists for α2, ß1 and ß3-adrenergic receptors decreased capsaicin activated currents and had no effect on ATP currents. Capsaicin currents were associated with increased neuronal excitability, while none of the adrenergic modulators produced change in rheobase. These results demonstrate that chronic adrenergic activation modulates two nociceptive transducer molecules, increasing or decreasing channel current depending on the adrenergic receptor subtype. These observations aid our understanding of nociceptive or antinociceptive effects of adrenergic agonists.
Subject(s)
Adrenergic Agonists , Capsaicin , Capsaicin/pharmacology , Adrenergic Agonists/pharmacology , Nociception , Ion Channels/pharmacology , Adenosine Triphosphate/pharmacology , Ganglia, Spinal , TRPV Cation ChannelsABSTRACT
Los canales de iones son glucoproteínas estructurales de la membrana celular que participan en la función, sobre todo de células excitables, para generar el potencial de acción y además ayudan a mantener el equilibrio de iones y de agua en los espacios intra y extracelulares. En la presente revisión se mencionan, entre otros aspectos, su estructura, los principios básicos de su función y algunas de las enfermedades hereditarias que ocurren habitualmente por una formación anormal de estas estructuras. La habilidad que tenemos de pensar y movernos depende de los cambios de voltaje iniciados por la movilización de iones, lo cual regula la función nerviosa y muscular. Por mucho tiempo se ha sabido que estos canales son blanco de manipulación por varios fármacos aplicados, sobre todo, a nivel de la clínica cardiovascular; otros medicamentos, usados ampliamente en forma secundaria, también pueden alterar la función de los canales induciendo efectos colaterales que pueden ser graves. Todos estos aspectos y algunos otros se mencionan en la presente revisión
Subject(s)
Calcium Channels/physiology , Ion Channels/pharmacology , Ion Channels/physiology , Ion Channels/genetics , Cell Membrane/physiology , Potassium Channels/physiologyABSTRACT
The effective size of colicin Ia channel was tested by a recently described method 9FEMS, Microbiology and Immunology (1992). 105: 93-100) in which the nonelectrolyte molecules with different hydrodynamic diameters (0.52 to 5.0nm) were used as molecular tools. We have shown that despite low conductance (55-105 pS at 1.5 MKCl, pH 7.0) the ion channels formed by colicin Ia have a fairly large water pore diameter equal to 1.66-1 1.88nm. The results are discussed in terms of an energetic barrier for ions passing into the channel lumen