Neurotransmitters and signalling

Chemical transmission at brain synapses is critical to neuronal signalling, and when it goes wrong, psychiatric or neurological disorder likely ensues. Chemical transmission was once considered to involve a simple ‘forward-direction’, on–off signal generated through the interaction between one of a small number of neurotransmitter molecules and their receptor. This concept has evolved to the synapse being viewed as an extremely complex chemical machine that utilizes a vast array of neurotransmitter-specific proteins to assemble, store, mobilize, and break down one or more of potentially hundreds of chemically diverse transmitter molecules. Individual molecules generate signals over different timescales and spatial domains by interacting with multiple receptor types. Moreover, rather than functioning through the use of a single neurotransmitter, most, if not all, synapses likely operate through the co-release of multiple neurotransmitters. Even the idea that signals are transmitted in a ‘forward direction’ is an oversimplification—certain neurotransmitters signal in the reverse direction. These issues, and more, are reviewed here.

Electrical coupling and its channels

As the physiology of synapses began to be explored in the 1950s, it became clear that electrical communication between neurons could not always be explained by chemical transmission. Instead, careful studies pointed to a direct intercellular pathway of current flow and to the anatomical structure that was (eventually) called the gap junction. The mechanism of intercellular current flow was simple compared with chemical transmission, but the consequences of electrical signaling in excitable tissues were not. With the recognition that channels were a means of passive ion movement across membranes, the character and behavior of gap junction channels came under scrutiny. It became evident that these gated channels mediated intercellular transfer of small molecules as well as atomic ions, thereby mediating chemical, as well as electrical, signaling. Members of the responsible protein family in vertebrates—connexins—were cloned and their channels studied by many of the increasingly biophysical techniques that were being applied to other channels. As described here, much of the evolution of the field, from electrical coupling to channel structure–function, has appeared in the pages of the Journal of General Physiology.

Identification of a vesicular ATP release inhibitor for the treatment of neuropathic and inflammatory pain

Despite the high incidence of neuropathic and inflammatory pain worldwide, effective drugs with few side effects are currently unavailable for the treatment of chronic pain. Recently, researchers have proposed that inhibitors of purinergic chemical transmission, which plays a key role in the pathological pain response, may allow for targeted treatment of pathological neuropathic and inflammatory pain. However, such therapeutic analgesic agents have yet to be developed. In the present study, we demonstrated that clodronate, a first-generation bisphosphonate with comparatively fewer side effects than traditional treatments, significantly attenuates neuropathic and inflammatory pain unrelated to bone abnormalities via inhibition of vesicular nucleotide transporter (VNUT), a key molecule for the initiation of purinergic chemical transmission. In vitro analyses indicated that clodronate inhibits VNUT at a half-maximal inhibitory concentration of 15.6 nM without affecting other vesicular neurotransmitter transporters, acting as an allosteric modulator through competition with Cl−. A low concentration of clodronate impaired vesicular ATP release from neurons, microglia, and immune cells. In vivo analyses revealed that clodronate is more effective than other therapeutic agents in attenuating neuropathic and inflammatory pain, as well as the accompanying inflammation, in wild-type but not VNUT−/− mice, without affecting basal nociception. These findings indicate that clodronate may represent a unique treatment strategy for chronic neuropathic and inflammatory pain via inhibition of vesicular ATP release.

The Endocrine System at a Glance: Problemas y técnicas de traducción en el capítulo Chemical Transmission

El discurso científico, en el que se enmarcan los textos médicos, persigue fines informativos, didácticos y comunicativos. Por ello, atiende a las siguientes particularidades: <em>a</em>) la veracidad, <em>b</em>) la precisión y <em>c</em>) la claridad (Navarro González, 2009). Sin embargo, persiste el uso de una sintaxis compleja, así como la utilización de elipsis, gerundios o incisos que pueden ser óbice para la comprensión del mensaje. En el presente trabajo se analizarán los principales problemas de traducción encontrados durante la actividad traductora del capítulo 2 del manual <em>The Endocrine System At aGlance </em>(2011), a los que se les dará solución mediante una determinada técnica de traducción (Hurtado Albir, 2011).

The Endocrine System at a Glance: Problemas y técnicas de traducción en el capítulo “Chemical Transmission”

El discurso científico, en el que se enmarcan los textos médicos, persigue fines informativos, didácticos y comunicativos. Por ello, atiende a las siguientes particularidades: a) la veracidad, b) la precisión y c) la claridad (Navarro González, 2009). Sin embargo, persiste el uso de una sintaxis compleja, así como la utilización de elipsis, gerundios o incisos que pueden ser óbice para la comprensión del mensaje. En el presente trabajo se analizarán los principales problemas de traducción encontrados durante la actividad traductora del capítulo 2 del manual The Endocrine System at a Glance (2011), a los que se les dará solución mediante una determinada técnica de traducción (Hurtado Albir, 2011).