68 research outputs found
Modeling the differentiation of A- and C-type baroreceptor firing patterns
The baroreceptor neurons serve as the primary transducers of blood pressure
for the autonomic nervous system and are thus critical in enabling the body to
respond effectively to changes in blood pressure. These neurons can be
separated into two types (A and C) based on the myelination of their axons and
their distinct firing patterns elicited in response to specific pressure
stimuli. This study has developed a comprehensive model of the afferent
baroreceptor discharge built on physiological knowledge of arterial wall
mechanics, firing rate responses to controlled pressure stimuli, and ion
channel dynamics within the baroreceptor neurons. With this model, we were able
to predict firing rates observed in previously published experiments in both A-
and C-type neurons. These results were obtained by adjusting model parameters
determining the maximal ion-channel conductances. The observed variation in the
model parameters are hypothesized to correspond to physiological differences
between A- and C-type neurons. In agreement with published experimental
observations, our simulations suggest that a twofold lower potassium
conductance in C-type neurons is responsible for the observed sustained basal
firing, whereas a tenfold higher mechanosensitive conductance is responsible
for the greater firing rate observed in A-type neurons. A better understanding
of the difference between the two neuron types can potentially be used to gain
more insight into the underlying pathophysiology facilitating development of
targeted interventions improving baroreflex function in diseased individuals,
e.g. in patients with autonomic failure, a syndrome that is difficult to
diagnose in terms of its pathophysiology.Comment: Keywords: Baroreflex model, mechanosensitivity, A- and C-type
afferent baroreceptors, biophysical model, computational mode
Identification of NKG2A and NKp80 as specific natural killer cell markers in rhesus and pigtailed monkeys
Investigations of natural killer (NK) cells in simian models of disease have been hampered by a lack of appropriate phenotypic markers and by an inadequate understanding of the regulation of NK cell activities. In the present study, a panel of monoclonal antibodies (mAbs) specific for various human NK receptors was screened for cross-reactivity with NK cells from rhesus macaques and pigtailed macaques. Flow cytometric analyses using anti-human NKG2A and anti-human NKp80 mAbs individually, and particularly in combination with anti-CD16 mAb, allowed for the identification of the entire NK cell population in both species. NK cells in monkeys were generally identified by negative selection of peripheral blood mononuclear cells (PBMCs) for the absence of T-cell, B-cell, and monocyte markers. mAb-mediated ligation of NKp80 induced NK cell cytotoxicity, while in the case of NKG2A it displayed a clear capability to inhibit the lysis of target cells by NK cells from macaques, as well as from humans. This new phenotypic and functional characterization of NKG2A and NKp80 in rhesus and pigtailed macaque NK cells provides a new approach in the analysis of their innate immune system. (Blood. 2005;106:1718-1725
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