Biomedical subjects

Gabriella B Lundkvist

Publications and source records attributed to Gabriella B Lundkvist.

4 recordsLinked to original sources

PubMed2005

A calcium flux is required for circadian rhythm generation in mammalian pacemaker neurons.

Generation of mammalian circadian rhythms involves molecular transcriptional and translational feedback loops. It is not clear how membrane events interact with the intracellular molecular clock or whether membrane activities are involved in the actual generation of the circadian rhythm. We examined the role of membrane potential and calcium (Ca2+) influx in the expression of the circadian rhythm of the clock gene Period 1 (Per1) within the rat suprachiasmatic nucleus (SCN), the master pacemaker controlling circadian rhythmicity. Membrane hyperpolarization, caused by lowering the extracellular concentration of potassium or blocking Ca2+ influx in SCN cultures by lowering [Ca2+], reversibly abolished the rhythmic expression of Per1. In addition, the amplitude of Per1 expression was markedly decreased by voltage-gated Ca2+ channel antagonists. A similar result was observed for mouse Per1 and PER2. Together, these results strongly suggest that a transmembrane Ca2+ flux is necessary for sustained molecular rhythmicity in the SCN. We propose that periodic Ca2+ influx, resulting from circadian variations in membrane potential, is a critical process for circadian pacemaker function.

Animals↗

PubMed2005

Role of neuronal membrane events in circadian rhythm generation.

Circadian clock systems are composed of an input or "entrainment" pathway by which synchronization to the external environment occurs, a pacemaker responsible for generating rhythmicity, and an output or "expression" pathway through which rhythmic signals act to modulate physiology and behavior. The circadian pacemaker contains molecular feedback loops of rhythmically expressed genes and their protein products, which, through interactions, generate a circa 24-h cycle of transcription and translation of clock and clock-controlled genes. Neuronal membrane events appear to play major roles in entrainment of circadian rhythms in mollusks and mammals. In mammals, the suprachiasmatic nuclei of the hypothalamus receive photic information via the retinohypothalamic tract. Retinal signals, mediated by glutamate, induce calcium release and activate a number of intracellular cascades involved in photic gating and phase shifting. Membrane events are also involved in rhythm expression. Calcium and potassium currents influence the electrical output of pacemaker neurons by altering shape and intervals of impulse prepotentials, afterhyperpolarization periods, and interspike intervals, as well as altering membrane potentials and thereby shaping the spontaneous rhythmic spiking patterns. Unlike the involvement of membrane events in circadian entrainment and expression, it is less clear whether electrical activity, postsynaptic events, and transmembrane ion fluxes also are essential elements in rhythm generation. Studies, however, suggest that neuronal membrane activity may indeed play a crucial role in circadian rhythm generation.

Action Potentials↗

PubMed2004

Why trypanosomes cause sleeping sickness.

African trypanosomiasis or sleeping sickness is hallmarked by sleep and wakefulness disturbances. In contrast to other infections, there is no hypersomnia, but the sleep pattern is fragmented. This overview discusses that the causative agents, the parasites Trypanosoma brucei, target circumventricular organs in the brain, causing inflammatory responses in hypothalamic structures that may lead to dysfunctions in the circadian-timing and sleep-regulatory systems.

Animals↗

PubMed2002

The suprachiasmatic nucleus exhibits diurnal variations in spontaneous excitatory postsynaptic activity.

A most prominent feature of neurons in the suprachiasmatic nucleus (SCN) is the circadian rhythm in spontaneous firing frequency. To disclose synaptic mechanisms associated with the rhythmic activity, the spontaneous postsynaptic activity was studied using whole-cell, patch clamp recordings in the ventral region of the SCN in slice preparations from rats. The synaptic events were compared between two time intervals corresponding to the highest and lowest electrical activity within the SCN during subjective daytime and nighttime, respectively. The gamma-aminobutyric acid (GABA)-mediated spontaneous inhibitory activity showed no diurnal variations, but the excitatory activity was markedly higher in frequency, without differences in amplitude, during the subjective day compared to the subjective night. Spontaneous and evoked inhibitory synaptic events were blocked by the GABA(A) receptor antagonist bicuculline. The alpha-amino-hydroxy-5-methylisoxazole-4-propionic acid (AMPA/kainate) receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) blocked most of the excitatory activity. In addition, CNQX reduced the spontaneous inhibitory activity. The N-methyl-D-aspartate antagonist D-2-amino-5-phosphonopentanoic acid reduced the inhibitory activity to a lesser degree, and there was no significant difference in amplitude or frequency of synaptic events in control and Mg2+-free solutions, indicating that the AMPA receptor plays an important role in regulating the inhibitory release of GABA within the SCN. Ipsi- and contralateral stimulation of the SCN consistently evoked excitatory synaptic responses. Inhibitory synaptic responses occurred in some neurons upon increasing stimulus strength. In conclusion, this study shows that there is a substantial influence from spontaneous glutamatergic synapses on the ventral part of the SCN and that these exhibit daily variations in activity. Diurnal fluctuations in spontaneous excitatory postsynaptic activity within this network may contribute to the mechanisms for synchronization of rhythms between individual SCN neurons and may underlie the daily variations in the spontaneous firing frequency of SCN neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗