Abstract
Role of BK and ASIC in the Activation of Glomus Cells by Extracellular Acidosis and Hypoxia
The FASEB journal, Vol.20(5), pp.A1230-A1230
03/2006
DOI: 10.1096/fasebj.20.5.A1230-b
Abstract
Depolarization of glomus cells of the carotid body in response to extracellular acidosis has been ascribed to a drop in intracellular pH. Our recent studies suggest that disruption of the acid‐sensitive ion channel 3 (ASIC3) suppresses the carotid chemoreflex in mice. In this study, we tested the effect of extracellular acidosis and hypoxia on isolated glomus cells while buffering intracellular pH with 10 mM Hepes. Whole cell patch clamping was used to measure either cell current or membrane potential. Extracellular acidosis caused a sustained pH‐dependent depolarization of 7.2±1.2, 10.7±1.5 and 18.4±3.3 mV at pH 7.0, 6.5 and 6.0, respectively (n = 5). In 9 cells, the response to a pH of 6.0 (17.2±1.9mV) was significantly greater than the effect of hypoxia (p02 = ~50mmHg), which depolarized only 5 of the 9 cells by 5.5±1.1 mV. Combined pH 6.0 and hypoxia had a simple additive effect (21.4±2.1mV, n = 5). Neither iberiotoxin (BK blocker, 200 nM) (n = 5) nor amiloride (ASIC blocker, 200 ìM) (n = 6) prevented the sustained depolarization at pH 6.0. However, iberiotoxin suppressed the response to hypoxia from 5.5±1.1 mV to 0.8±0.6 mV (n = 5), and in one cell amiloride blocked a transient initial depolarization of 45 mV seen at pH 7.0. Under voltage clamp, acidosis induced transient inward currents (64±19 pA) (n = 9) that were reversibly blocked in three cells treated with amiloride. We conclude that 1) extracellular acidosis depolarizes glomus cells directly and to a greater extent than hypoxia at constant intracellular pH; 2) the effects of low pH and hypoxia appear additive not synergistic; 3) the response to hypoxia appears dependent on BK; and 4) ASIC channels may mediate the transient inward current during acidosis. [HL 14388]
Details
- Title: Subtitle
- Role of BK and ASIC in the Activation of Glomus Cells by Extracellular Acidosis and Hypoxia
- Creators
- Zhi‐Yong Tan - Univ. of IowaCarol A. Whiteis - University of IowaYongjun Lu - University of IowaMark W. Chapleau - University of IowaFrancois M. Abboud - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(5), pp.A1230-A1230
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.5.A1230-b
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine; Stead Family Department of Pediatrics; Critical Care
- Record Identifier
- 9984303002202771
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