Biomedical subjects

H S Lopez

Publications and source records attributed to H S Lopez.

4 recordsLinked to original sources

PubMed1992

Kinetics of G protein-mediated modulation of the potassium M-current in bullfrog sympathetic neurons.

The inhibition of the voltage-dependent, K+ M-current (IM) following receptor-independent G protein activation with controlled intracellular perfusion of nonhydrolyzable GTP analogs had an exponential time course, with rates hyperbolically dependent on GTP analog concentration, and a limiting value of 0.53 min-1. The inhibitory agonist muscarine caused a concentration-dependent acceleration of the rate of nucleotide-induced inhibition, with a plateau of about 20 min-1 and an exponential time course. In neurons not treated with nucleotide analogs the IM recovery rate following agonist removal was 3-7 min-1. It is proposed that the overall kinetics of the transduction pathway for IM modulation is governed by the agonist-dependent kinetics of nucleotide interaction with G proteins. A simple model of IM modulation based on G proteins' kinetics has been developed. These data suggest a possible cellular process responsible for the time course of slow synaptic potentials caused by IM inhibition in sympathetic neurons.

Animals↗

PubMed1992

Neuromodulation.

The ability of the nervous system to respond to the environment and to learn depends upon the tuning of neuronal electrical activity, loosely called neuromodulation. The substrates for electrical activity and, therefore, neuromodulation are ion channels which may be either synaptic or extrasynaptic. Neuromodulation is dynamic and most frequently involves neurotransmitters and hormones acting via G-protein-coupled pathways.

Animals↗

PubMed1991

Correlation between G protein activation and reblocking kinetics of Ca2+ channel currents in rat sensory neurons.

Membrane depolarization relieves the G protein-mediated inhibition or block of high threshold Ca2+ channel currents. We found that the net rate of reblocking depended on the extent of G protein activation. With low intracellular concentrations of GTP gamma S reblocking rates resembled inactivation rates; with higher concentrations reblocking rates increased progressively. Reblocking kinetics were fit with a sum of two exponential functions having time constants (in ms) tau F greater than or equal to 10 and tau S greater than or equal to 30. Unblock during depolarization was fit by a single exponential function with time constant tau A similar to tau F. A model was developed in which unblocking followed dissociation of a blocking molecule, possibly the G protein itself, from Ca2+ channels, and reblocking occurred at rates that depended on the concentration of the blocking molecule. The time course of Ca2+ entry and thus presynaptic Ca2+ levels can be regulated by both the concentration of the G-protein-dependent blocking particle and membrane potential.

Animals↗

PubMed1990

Associative synaptic potentiation and depression: quantification of dissociable modifications in the hippocampal dentate gyrus favors a particular class of synaptic modification equations.

This report further characterizes associative long-term synaptic modification of the ipsilateral and contralateral synapses formed by the bilateral entorhinal cortical (EC) projection to the dentate gyrus (DG). The experimental model is the anesthetized hooded rat. The quantitative results qualify this system as a model for studying the rules of associative synaptic modification formulated in terms of individual synapses. Bilateral DG microelectrodes recorded both ipsilateral and contralateral EC-DG responses before and after brief, high-frequency EC conditioning stimulation. The weak contralateral pathway received high-frequency conditioning before, during, or after similar conditioning of the strong, converging ipsilateral pathway. Statistical analyses revealed two types of significant, dissociated synaptic modifications, which depend on the relationship of the ipsilateral and contralateral afferents. First, contralateral EC-DG responses potentiated or depressed when the converging ipsilateral responses concurrently either potentiated or remained unchanged. Second, contralateral EC-DG responses potentiated, depressed, or showed no change when the collateral ipsilateral responses concurrently either potentiated or remained unchanged. Correlation and contingency table analyses indicated that changes in the contralateral synaptic responses are not well predicted by changes at either neighboring synapses of the converging ipsilateral pathway or at synapses of the collateral ipsilateral pathway. The contingencies of associated pre- and postsynaptic activation determined by the conditioning paradigm, however, accurately predicted the altered synaptic responses of both ipsilateral and contralateral EC-DG pathways. The results imply that associative synaptic modification in the EC-DG system is specific to individual synapses and requires both appropriate presynaptic and postsynaptic activation. Because this system provides suitable controls for nonspecific effects of conditioning stimulation and because modification of neighboring synapses is dissociable, the EC-DG system can be used to study further those rules of activity-dependent associative modification that are formulated in terms of individual synapses. The discussion briefly considers published rules of synaptic modification, pointing out several rules that are not consistent with the experimental observations and one that agrees with the present results.

Animals↗