Calcium- and Voltage-Dependent Dual Gating ANO1 is an Intrinsic Determinant of Repolarization in Rod Bipolar Cells of the Mouse Retina.
Cells
; 9(3)2020 02 26.
Article
em En
| MEDLINE
| ID: mdl-32110998
ABSTRACT
TMEM16A/anoctamin1 (ANO1), a calcium (Ca2+)-activated chloride (Cl-) channel, has many functions in various excitable cells and modulates excitability in both Ca2+- and voltage-gating modes. However, its gating characteristics and role in primary neural cells remain unclear. Here, we characterized its Ca2+- and voltage-dependent components in rod bipolar cells using dissociated and slice preparations of the mouse retina. The I-V curves of Ca2+-dependent ANO1 tail current and voltage-gated Ca2+ channel (VGCC) are similar; as ANO1 is blocked by VGCC inhibitors, ANO1 may be gated by Ca2+ influx through VGCC. The voltage-dependent component of ANO1 has outward rectifying and sustained characteristics and is clearly isolated by the inhibitory effect of Cl- reduction and T16Ainh-A01, a selective ANO1 inhibitor, in high EGTA, a Ca2+ chelator. The voltage-dependent component disappears due to VGCC inhibition, suggesting that Ca2+ is the essential trigger for ANO1. In perforated current-clamping method, the application of T16Ainh-A01 and reduction of Cl- extended excitation periods in rod bipolar cells, revealing that ANO1 induces repolarization during excitation. Overall, ANO1 opens by VGCC activation during physiological excitation of the rod bipolar cell and has a voltage-dependent component. These two gating-modes concurrently provide the intrinsic characteristics of the membrane potential in rod bipolar cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativação do Canal Iônico
/
Cálcio
/
Eletricidade
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Células Bipolares da Retina
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Anoctamina-1
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cells
Ano de publicação:
2020
Tipo de documento:
Article