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Glial contribution to the modulation of preBötzinger Complex rhythm generating networks by ATP
Author(s) -
Huxtable Adrianne G,
Zwicker Jennifer D,
Alvares Tuca S,
Ruangkittisakul Araya,
Fang X,
Ballanyi Klaus,
Funk Gregory D
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.960.13
Subject(s) - glutamine synthetase , biophysics , biology , brainstem , receptor , microbiology and biotechnology , chemistry , biochemistry , neuroscience , glutamine , amino acid
Activation of P2Y 1 receptors in the preBötzinger Complex (preBötC) potently increases frequency (f) (J Neurosci, 27, 993‐05, '07). This could reflect the ubiquitous but weak sensitivity of preBötC neurons to ATP (J Physiol, 586, 129‐46, '08). The present study used rhythmic medullary brainstem slices from neonatal rats to test if glial cells contribute to the ATP‐evoked f increase. Control ATP responses were compared to those after glial function was disrupted by bath‐applied glial toxins (>60 min, fluoroacetate, FA, or methionine sulfoximine, MSO), and rhythm restored with glutamine (1.5 mM). In control, f doubled in response to ATP (0.1 mM, 10 s). However in toxin, ATP was either without effect (MSO, n=7), or 1.5‐fold less potent (FA, n=10). Substance‐P responses were unaffected by the toxins. We next tested whether the glial contribution could involve their direct sensitivity to ATP. Two‐photon imaging of fluo‐4 Ca 2+ fluorescence revealed small cells in the preBötC with somatic areas = 100 μm 2 (n=126, 5 slices) are sensitive to bath‐applied ATP (0.1 mM). Whole‐cell recordings confirmed the presence of small, non‐excitable, low input resistance (23±2 MO) cells in this region are ATP‐sensitive (n=4). These data indicate that glial cells contribute to the f increase evoked by ATP in the preBötC, and that glial P2 receptors are likely involved. Supported by NSERC, CIHR‐MFN, CIHR, AHFMR, CFI, ASRA.