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Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
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Target Concepts:
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Query: UMLS:C0020440 (
hypercapnia
)
7,939
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Intracellular chloride ([Cl
-
]
i
) and pH (pH
i
) are fundamental regulators of neuronal excitability. They exert wide-ranging effects on synaptic signaling and plasticity and on development and disorders of the brain. The ideal technique to elucidate the underlying ionic mechanisms is quantitative and combined two-photon imaging of [Cl
-
]
i
and pH
i
, but this has never been performed at the cellular level in vivo. Here, by using a genetically encoded fluorescent sensor that includes a spectroscopic reference (an element insensitive to Cl
-
and pH), we show that ratiometric imaging is strongly affected by the optical properties of the brain. We have designed a method that fully corrects for this source of error. Parallel measurements of [Cl
-
]
i
and pH
i
at the single-cell level in the mouse cortex showed the in vivo presence of the widely discussed developmental fall in [Cl
-
]
i
and the role of the
K-Cl cotransporter
KCC2 in this process. Then, we introduce a dynamic two-photon excitation protocol to simultaneously determine the changes of pH
i
and [Cl
-
]
i
in response to
hypercapnia
and seizure activity.
...
PMID:Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo. 2897 89
