Biomedical subjects

Cecilia Vergara

Publications and source records attributed to Cecilia Vergara.

5 recordsLinked to original sources

PubMed2006

Divalent cations as modulators of neuronal excitability: emphasis on copper and zinc.

Based on indirect evidence, a role for synaptically released copper and zinc as modulators of neuronal activity has been proposed. To test this proposal directly, we studied the effect of copper, zinc, and other divalent cations on voltage-dependent currents in dissociated toad olfactory neurons and on their firing rate induced by small depolarizing currents. Divalent cations in the nanomolar range sped up the activation kinetics and increased the amplitude of the inward sodium current. In the micromolar range, they caused a dose dependent inhibition of the inward Na+ and Ca2+ currents (INa and ICa) and reduced de amplitude of the Ca2+-dependent K+ outward current (ICa-K). On the other hand, the firing rate of olfactory neurons increased when exposed to nanomolar concentration of divalent cations and decreased when exposed to micromolar concentrations. This biphasic effect of divalent cations on neuronal excitability may be explained by the interaction of these ions with high and low affinity sites in voltage-gated channels. Our results support the idea that these ions are normal modulators of neuronal excitability.

Action Potentials↗

PubMed2004

CNTF, a pleiotropic cytokine: emphasis on its myotrophic role.

Ciliary neurotrophic factor (CNTF) is a cytokine whose neurotrophic and differentiating effects over cells in the central nervous system (CNS) have been clearly demonstrated. This article summarizes the general characteristics of CNTF, its receptor and the signaling pathway that it activates and focuses on its effects over skeletal muscle, one of its major target tissues outside the central nervous system. The evidence for the existence of other molecules that signal through the same complex as CNTF is also reviewed.

Animals↗

PubMed2003

Ciliary neurotrophic factor (CNTF) affects the excitable and contractile properties of innervated skeletal muscles.

The well-established trophic role of CNTF upon neurons led to performing clinical trials in patients of neurodegenerative diseases. However, trials were suspended due to side effects such as severe weight loss, hyperalgesia, coughing, muscle cramps and pain. So far it is not known how CNTF triggers the problems related to skeletal muscle cramps and pain. CNTF has also been described as a myotrophic factor for denervated skeletal muscles, but the possibility that it affects innervated muscles has also been considered. Since a myotrophic factor could be a valuable tool for treatment of several muscle diseases, we studied the effects of low doses of CNTF delivered systemically by an osmotic pump, over the electrical and mechanical properties of innervated and denervated fast and slow muscles. CNTF induced spontaneous electrical discharges and slowed twitches in innervated muscles, but did not prevent the changes induced by denervation. We postulate that the spontaneous discharges induced by CNTF in innervated muscles may be the cause of the cramps, coughing, and muscle ache reported by patients. At low doses, CNTF does not exert its myotrophic role over denervated muscles but clearly affects the excitable and contractile properties of innervated muscles.

Animals↗

PubMed2002

Permeability changes induced by polylysines in rat spermatids.

High molecular weight (HMW, >15 kDa) but not low molecular weight (LMW, <15 kDa) polylysines (PLs) bound and induced permeability changes in rat spermatid plasma membranes, estimated by Mn2+ quenching of intracellular indo-1 fluorescence (K(1/2) = 3.3 +/- 0.5 microg/ml) and Co2+ quenching of intracellular calcein. The pharmacology of the Mn2+ entry pathway activated by HMW PL does not suggest that Ca2+ channels are involved in this phenomenon. Concentrations of HMW PL that induced divalent ion entry did not induce the entry of ethidium bromide, suggesting that HMW PL first bound and perturbed the plasma membrane structure inducing a non-specific increase in membrane permeability. High concentrations of HMW PL induced cell lysis (K(1/2) = 23 microg/ml). The binding of HMW PL, initially homogenous on the cell surface, subsequently progressed to a segregated pattern resembling a clustering phenomenon.

Animals↗

PubMed2002

Ca(2+)-activated K+ channel inhibition by reactive oxygen species.

We studied the effect of H(2)O(2) on the gating behavior of large-conductance Ca(2+)-sensitive voltage-dependent K(+) (K(V,Ca)) channels. We recorded potassium currents from single skeletal muscle channels incorporated into bilayers or using macropatches of Xenopus laevis oocytes membranes expressing the human Slowpoke (hSlo) alpha-subunit. Exposure of the intracellular side of K(V,Ca) channels to H(2)O(2) (4-23 mM) leads to a time-dependent decrease of the open probability (P(o)) without affecting the unitary conductance. H(2)O(2) did not affect channel activity when added to the extracellular side. These results provide evidence for an intracellular site(s) of H(2)O(2) action. Desferrioxamine (60 microM) and cysteine (1 mM) completely inhibited the effect of H(2)O(2), indicating that the decrease in P(o) was mediated by hydroxyl radicals. The reducing agent dithiothreitol (DTT) could not fully reverse the effect of H(2)O(2). However, DTT did completely reverse the decrease in P(o) induced by the oxidizing agent 5,5'-dithio-bis-(2-nitrobenzoic acid). The incomplete recovery of K(V,Ca) channel activity promoted by DTT suggests that H(2)O(2) treatment must be modifying other amino acid residues, e.g., as methionine or tryptophan, besides cysteine. Noise analysis of macroscopic currents in Xenopus oocytes expressing hSlo channels showed that H(2)O(2) induced a decrease in current mediated by a decrease both in the number of active channels and P(o).

Animals↗