Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?
Am J Physiol Renal Physiol
; 304(5): F491-7, 2013 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-23283993
ABSTRACT
Sensory neurons with afferent axons from the kidney are extraordinary in their response to electrical stimulation. More than 50% exhibit a tonic firing pattern, i.e., sustained action potential firing throughout depolarizing, pointing to an increased excitability, whereas nonrenal neurons show mainly a phasic response, i.e., less than five action potentials. Here we investigated whether these peculiar firing characteristics of renal afferent neurons are due to differences in the expression of voltage-gated sodium channels (Navs). Dorsal root ganglion (DRG) neurons from rats (Th11-L2) were recorded by the current-clamp technique and distinguished as "tonic" or "phasic." In voltage-clamp recordings, Navs were characterized by their tetrodotoxoxin (TTX) sensitivity, and their molecular identity was revealed by RT-PCR. The firing pattern of 66 DRG neurons (41 renal and 25 nonrenal) was investigated. Renal neurons exhibited more often a tonic firing pattern (56.1 vs. 12%). Tonic neurons showed a more positive threshold (-21.75 ± 1.43 vs.-29.33 ± 1.63 mV; P < 0.05), a higher overshoot (56.74 [53.6-60.96] vs. 46.79 mV [38.63-54.75]; P < 0.05) and longer action potential duration (4.61 [4.15-5.85] vs. 3.35 ms [2.12-5.67]; P < 0.05). These findings point to an increased presence of the TTX-resistant Navs 1.8 and 1.9. Furthermore, tonic neurons exhibited a relatively higher portion of TTX-resistant sodium currents. Interestingly, mRNA expression of TTX-resistant sodium channels was significantly increased in renal, predominantly tonic, DRG neurons. Hence, under physiological conditions, renal sensory neurons exhibit predominantly a firing pattern associated with higher excitability. Our findings support that this is due to an increased expression and activation of TTX-resistant Navs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Receptoras Sensoriais
/
Canais de Sódio Disparados por Voltagem
/
Gânglios Espinais
/
Rim
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Renal Physiol
Assunto da revista:
FISIOLOGIA
/
NEFROLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Alemanha