Biomedical subjects

Ricardo Felix

Publications and source records attributed to Ricardo Felix.

22 records · Page 2Linked to original sources

PubMed2002

Long-term regulation of voltage-gated Ca(2+) channels by gabapentin.

Gabapentin (GBP) is a gamma-aminobutyric acid analog effective in the treatment of seizures. A high-affinity interaction between GBP and the alpha(2)delta subunit of the voltage-gated Ca(2+) channels has been documented. In this report, we examined the effects of the chronic treatment with GBP on neuronal recombinant P/Q-type Ca(2+) channels expressed in Xenopus oocytes. GBP did not affect significantly the amplitude or the voltage dependence of the currents. Exposure to the drug did, however, slow down the kinetics of inactivation in a dose-dependent fashion. In addition, biochemical analysis showed that the integrity of Ca(2+) channel complex is not apparently affected by GBP binding, suggesting that chronic treatment with the drug might cause the channel kinetic modification through subtle conformational changes of the protein complex.

Acetates↗

PubMed2002

Identification of distinct K+ channels in mouse spermatogenic cells and sperm.

Potassium (K+) channels are believed to regulate mammalian sperm acquisition of fertilising capacity. However, the molecular identity of these proteins in sperm has not been elucidated. In this report, using immunoconfocal and electron microscopy we show that a minimum of four different classes of K+ channels (Kv1.1, Kv1.2, Kv3.1 and GIRK1) are present and regionally distributed over the surface of mouse epididymal sperm. In addition, the use of reverse transcription polymerase chain reaction on RNA from mouse spermatogenic cells allowed the amplification of multiple transcripts corresponding to the channels identified by immunocytochemistry. Consistent with this, whole-cell patch-clamp recordings showed the expression of at least two different outwardly rectifying K+ currents in spermatogenic cells.

Animals↗

PubMed2002

Insights from mouse models of absence epilepsy into Ca2+ channel physiology and disease etiology.

1. Changes in intracellular Ca2+ ([Ca2+]i) levels provide signals that allow neurons to respond to a host of external stimuli. A major mechanism for elevating [Ca2+]i is the influx of extracellular Ca2+ through voltage-gated channels (Ca(V)) in the plasma membrane. Malfunction in Ca(V) due to mutations in genes encoding channel proteins are increasingly being implicated in causing disease conditions, termed channelopathies. 2. Seven spontaneous mutations with cerebellar ataxia and generalized absence epilepsy have been identified in mice (tottering, leaner, rolling Nagoya, rocker, lethargic, ducky, and stargazer), and these overlapping phenotypes are directly related to mutations in genes encoding the four separate subunits that together form the multimeric neuronal Ca(V) complex. 3. The discovery and systematic analysis of these animal models is helping to clarify how different mutations affect channel function and how altered channel function produces disease.

Animals↗

PubMed2002

Down-regulation of N-type voltage-activated Ca2+ channels by gabapentin.

1. Although the cellular and molecular mechanisms of the anticonvulsant action of gabapentin (GBP) remain incompletely described, in vitro studies have shown that GBP binds to the alpha2delta subunit of the high voltage-activated (HVA) Ca2+ channels. 2. In this report, we analyzed the effects of GBP on the functional expression of HVA Ca2+ channels in the PC12 cell line model system. Negligible inhibition of Ca2+ channel activity was observed after acute treatment, but a significant decrease in Ca2+ current amplitude was promoted by chronic exposure to GBP. 3. Consistent with this, radioligand binding experiments showed a comparable reduction in the total number of membrane HVA N-type channels after GBP treatment.

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