Identification of subunits of voltage-gated calcium channels and actions of pregabalin on intrinsic primary afferent neurons in the guinea-pig ileum

2010 ◽  
Vol 22 (10) ◽  
pp. e301-e308 ◽  
Author(s):  
K. Needham ◽  
R. Bron ◽  
B. Hunne ◽  
T. V. Nguyen ◽  
K. Turner ◽  
...  
2013 ◽  
Vol 7 (31) ◽  
pp. 2293-2299 ◽  
Author(s):  
Carolina de Carvalho Correia Ana ◽  
L Cibeacute rio ◽  
Macecirc do im ◽  
de Souza Monteiro Fabio ◽  
Alves de Oliveira Gislaine ◽  
...  

2010 ◽  
Vol 65 (9-10) ◽  
pp. 627-636
Author(s):  
Fabiana de A. Cavalcante ◽  
Fabio De S. Monteiro ◽  
Italo Rossi R. Martins ◽  
Ticiano P. Barbosa ◽  
Celso de A Camara ◽  
...  

The present study was designed to further evaluate a possible spasmolytic activity of synthetic lapachol derivatives, norlapachol, α-norlapachone, β-norlapachone and hydro-hydroxy- norlapachol (HH-norlapachol), on guinea-pig ileum. In guinea-pig ileum, except for norlapachol, all naphthoquinones inhibited the phasic contractions induced by carbachol or histamine. Even when the ileum was pre-contracted with KCl, carbachol or histamine, all naphthoquinones induced relaxation, suggesting that these naphthoquinones could be acting on the voltage-gated calcium channels (CaV). As the tonic component this contraction is maintained mainly by the opening of the CaV, we hypothesized that these naphthoquinones might be acting on these channels. This hypothesis was confirmed by the observation that norlapachol (pD’2 = 4.99), α-norlapachone (pD’2 = 4.49), β-norlapachone (pD’2 = 6.33), and HH-norlapachol (pD’2 = 4.53) antagonized the contractions induced by CaCl2 in depolarizing medium nominally without Ca2+. As β-norlapachone was the most potent we decided to continue the study of its action mechanism. The fact that this naphthoquinone has inhibited the tonic contractions induced by S-(-)-Bay K8644 [EC50 = (1.6 ± 0.30) · 10-5 M] suggests that the Ca2+ channel involved belongs to the type L (CaV1.2). In addition, in the functional level, the spasmolytic effect of β-norlapachone does not involve participation of free radicals, since its curve of relaxation was unchanged in the presence of glutathione, an antioxidant agent.


2008 ◽  
Vol 18 (2) ◽  
pp. 183-189 ◽  
Author(s):  
Fabiana A. Cavalcante ◽  
Joelmir L. V. Silva ◽  
Viviane M. N. Carvalho ◽  
Celso A. Camara ◽  
Tania M. S. Silva ◽  
...  

1997 ◽  
Vol 77 (1) ◽  
pp. 299-308 ◽  
Author(s):  
Geoffrey M. Bove ◽  
Michael A. Moskowitz

Bove, Geoffrey M. and Michael A. Moskowitz. Primary Afferent Neurons Innervating Guinea Pig Dura. J. Neurophysiol. 77: 299–308, 1997. We made recordings from filaments of guinea pig nasociliary nerve to study response properties of afferent axons innervating the anterior superior sagittal sinus and surrounding dura mater. We analyzed 38 units in 14 experiments. Units were initially located with the use of mechanical stimuli, and were then characterized by their conduction velocity and sensitivities to mechanical, thermal, and chemical stimuli. Single-unit recordings revealed innervation of dura and superior sagittal sinus by slowly conducting axons, mostly in the unmyelinated range. The receptive fields were 1–30 mm2, and typically had one to three punctate spots of highest sensitivity. All units tested responded to topical application of chemical agents. Ninety-seven percent of units responded to 10−5 M capsaicin, 79% responded to a mixture of inflammatory mediators, and 37% responded to an acidic buffer (pH 5). These data underline the importance of chemical sensitivity in intracranial sensation. Heat and cold stimuli evoked responses in 56 and 41% of units tested, respectively. Although the response patterns during heating were typical of polymodal nociceptors innervating other tissues, the thresholds were lower than for other tissues (32.3–42°C). Cooling led to a phasic discharge, with thresholds between 25 and 32°C. Although units had different combinations of responses to mechanical, chemical, and thermal stimuli, when grouped by their sensitivities the groups did not differ regarding mechanical thresholds or presence of ongoing activity. This suggests that meningeal primary afferents are relatively homogeneous. Sensitivities of these units are in general consistent with nociceptors, although the thermal thresholds differ. These data provide the first detailed report of response properties of intracranial primary afferent units, likely to be involved in transmission of nociception and possibly mediation of intracranial pain.


1990 ◽  
Vol 64 (1) ◽  
pp. 91-104 ◽  
Author(s):  
R. E. Fisher ◽  
R. Gray ◽  
D. Johnston

1. The properties of single voltage-gated calcium channels were investigated in acutely exposed CA3 and CA1 pyramidal neurons and granule cells of area dentata in the adult guinea pig hippocampal formation. 2. Guinea pig hippocampal slices were prepared in a conventional manner, then treated with proteolytic enzymes and gently shaken to expose the somata of the three cell types studied. Standard patch-clamp techniques were used to record current flow through calcium channels in cell-attached membrane patches with isotonic barium as the charge carrier. 3. Single-channel current amplitudes were measured at different membrane potentials. Single-channel current-voltage plots were constructed and single-channel slope conductances were found to fall into three classes. These were (approximately) 8, 14, and 25 pS, and were observed in all three cell types. 4. The three groups of channels differed from each other in voltage dependence of activation: from a holding potential of -80, the small-conductance channel began to activate at about -40 to -30 mV, the medium-conductance channel at about -20 mV, and the large-conductance channel at approximately 0 mV. 5. Ensemble averages of single-channel currents during voltage steps revealed differences in voltage-dependent inactivation. The small-conductance channel inactivated completely within approximately 50 ms during steps from -80 to -10 mV or more positive. Steps to less positive potentials resulted in less inactivation. The medium-conductance channel displayed variable inactivation during steps from -80 to 0 mV. Inactivation of this channel during a 160-ms step ranged from virtually zero to approximately 100%. The large-conductance channel displayed no significant inactivation during steps as long as 400 ms. 6. The large-conductance channel was strikingly affected by the dihydropyridine agonist Bay K8644 (0.5-2.0 microM), resulting in a high probability of channel opening, prolonged openings, and an apparent increase in the number of channels available for activation. The medium and small-conductance channels were not noticeably affected by the drug. 7. The large-conductance channel could be induced to open at very negative membrane potentials by holding the patch for several seconds at 20 or 30 mV and stepping to -30 or -40 mV. This process was enhanced by Bay K8644, resulting in prolonged openings at potentials as negative as -100 mV.(ABSTRACT TRUNCATED AT 400 WORDS)


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