TY - JOUR
T1 - Properties of the proton-evoked currents and their modulation by Ca 2+ and Zn2+ in the acutely dissociated hippocampus CA1 neurons
AU - Gao, Jun
AU - Wu, Long Jun
AU - Xu, Lin
AU - Xu, Tian Le
N1 - Funding Information:
This study was supported by the National Basic Research Program of China (G1999054000), the National Natural Science Foundation of China (Nos. 30125015, 30321002 and 30228020) and the Knowledge Innovation Project from the Chinese Academy of Sciences (KSCX 2-SW-217) to T.-L. Xu.
PY - 2004/8/13
Y1 - 2004/8/13
N2 - The characterization of acid-sensing ion channel (ASIC)-like currents has been reported in hippocampal neurons in primary culture. However, it is suggested that the profile of expression of ASICs changes in culture. In this study, we investigated the properties of proton-activated current and its modulation by extracellular Ca2+ and Zn2+ in neurons acutely dissociated from the rat hippocampal CA1 using conventional whole-cell patch-clamp recording. A rapidly decaying inward current and membrane depolarization was induced by exogenous application of acidic solution. The current was sensitive to the extracellular proton with a response threshold of pH 7.0-6.8 and the pH50 of 6.1, the reversal potential close to the Na+ equilibrium potential. It had a characteristic of acid-sensing ion channels (ASICs) as demonstrated by its sensitivity to amiloride (IC 50=19.6±2.1 μM). Either low [Ca2+]o or high [Zn2+]o increased the amplitude of the current. All these characteristics are consistent with a current mediated through a mixture of homomeric ASIC1a and heteromeric ASIC1a+2a channels and closely replicate many of the characteristics that have been previously reported for hippocampal neurons cultured for a week or more, indicating that culture artifacts do not necessarily flaw the properties of ASICs. Interestingly, we found that high [Zn2+]o (>10-4 M) slowed the decay time constant of the ASIC-like current significantly in both acutely dissociated and cultured hippocampal neurons. In addition, the facilitating effects of low [Ca2+]o and high [Zn2+] o on the ASIC-like current were not additive. Since tissue acidosis, extracellular Zn2+ elevation and/or Ca2+ reduction occur concurrently under some physiological and/or pathological conditions, the present observations suggest that hippocampal ASICs may offer a novel pharmacological target for therapeutic invention.
AB - The characterization of acid-sensing ion channel (ASIC)-like currents has been reported in hippocampal neurons in primary culture. However, it is suggested that the profile of expression of ASICs changes in culture. In this study, we investigated the properties of proton-activated current and its modulation by extracellular Ca2+ and Zn2+ in neurons acutely dissociated from the rat hippocampal CA1 using conventional whole-cell patch-clamp recording. A rapidly decaying inward current and membrane depolarization was induced by exogenous application of acidic solution. The current was sensitive to the extracellular proton with a response threshold of pH 7.0-6.8 and the pH50 of 6.1, the reversal potential close to the Na+ equilibrium potential. It had a characteristic of acid-sensing ion channels (ASICs) as demonstrated by its sensitivity to amiloride (IC 50=19.6±2.1 μM). Either low [Ca2+]o or high [Zn2+]o increased the amplitude of the current. All these characteristics are consistent with a current mediated through a mixture of homomeric ASIC1a and heteromeric ASIC1a+2a channels and closely replicate many of the characteristics that have been previously reported for hippocampal neurons cultured for a week or more, indicating that culture artifacts do not necessarily flaw the properties of ASICs. Interestingly, we found that high [Zn2+]o (>10-4 M) slowed the decay time constant of the ASIC-like current significantly in both acutely dissociated and cultured hippocampal neurons. In addition, the facilitating effects of low [Ca2+]o and high [Zn2+] o on the ASIC-like current were not additive. Since tissue acidosis, extracellular Zn2+ elevation and/or Ca2+ reduction occur concurrently under some physiological and/or pathological conditions, the present observations suggest that hippocampal ASICs may offer a novel pharmacological target for therapeutic invention.
KW - Acid-sensing ion channel
KW - Cellular and molecular biology
KW - Hippocampal CA1 neuron
KW - Membrane composition and cell-surface macromolecules
KW - Patch-clamp
KW - Proton-induced current
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U2 - 10.1016/j.brainres.2004.05.046
DO - 10.1016/j.brainres.2004.05.046
M3 - Article
C2 - 15261115
AN - SCOPUS:3142751119
SN - 0006-8993
VL - 1017
SP - 197
EP - 207
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -