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The Journal of Neurophysiology Vol. 88 No. 2 August 2002, pp. 604-612
Copyright ©2002 by the American Physiological Society
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106
Summers, Beth A.,
Jeffrey L. Overholt, and
Nanduri R. Prabhakar.
CO2 and pH Independently Modulate L-Type
Ca2+ Current in Rabbit Carotid Body Glomus Cells. J. Neurophysiol. 88: 604-612, 2002. The carotid bodies respond to changes in arterial
O2, CO2, and pH, and
Ca2+ influx via voltage-gated
Ca2+ channels is an important step in the
chemoreception process. The objectives of the present study were as
follows: 1) to determine whether hypercapnia modulates
Ca2+ current in glomus cells, and if so, to
determine if this modulation is secondary to changes in pH;
2) to examine the mechanism of CO2
modulation of the Ca2+ current; and 3)
to determine whether the effects of hypercapnia and hypoxia on
Ca2+ channel activity in glomus cells are
synergistic. The effects of CO2 on
Ca2+ current were monitored in glomus cells
isolated from rabbit carotid bodies using both perforated and
conventional patch-clamp techniques. Raising CO2
in the extracellular solution from 5 to 10% (hypercapnia) reversibly
augmented the whole-cell Ca2+ current. This
augmentation was rapid and increased the whole-cell Ca2+ current similarly in both the perforated and
the conventional patch configurations by 16 ± 2%
(n = 5) and 15 ± 1% (n = 32), respectively. The following observations suggest that the effects of
CO2 are not secondary to changes in pH:
1) isohydric hypercapnia (pH maintained at 7.4) augmented
the Ca2+ current by 24 ± 2%
(n = 6); 2) decreasing the pH of the extra- or intracellular solutions decreased the Ca2+
current by 43 ± 4% (n = 8) and 13 ± 1%
(n = 5), respectively; and 3) hypercapnia
did not shift the half-maximal activation voltage (V1/2), whereas intracellular
and extracellular acidosis alone caused shifts in
V1/2. Furthermore, 100 nM of a
membrane-permeable protein kinase A inhibitor prevented the
augmentation by CO2, and 500 µM 8-Br-cAMP
mimicked the effect of CO2 by augmenting the
Ca2+ current by 10 ± 2% (n = 6). Also, cyclic AMP levels in carotid bodies increased from
1.98 ± 0.6 to 9.0 ± 2 pmol/µg protein in response to
hypercapnia. In contrast, decreasing pH in the nominal absence of
CO2 did not affect cAMP levels in rabbit carotid
bodies. Further, nisoldipine, but not 
-conotoxin MVIIC, prevented
augmentation of the Ca2+ current by
CO2. In addition, when combined, hypercapnia and
hypoxia augmented the Ca2+ current by 26 ± 4% (n = 7), which is greater than either stimulus alone, suggesting the effects are additive. Taken together, these results indicate that L-type Ca2+ current is
augmented by hypercapnia. The effect of CO2 is
not secondary to changes in pH and seems to be mediated by a protein kinase A-dependent mechanism. Furthermore, hypercapnia and hypoxia act
additively in stimulating Ca2+ current in glomus cells.
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