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Emerging Concepts in Ion Channel Biophysics
Poster Abstracts
95
15-POS
Board 15
Minocycline Inhibits ASIC Currents in Dorsal Root Ganglion Neurons by a Selective
Action on the ASIC1a Channel Subunit
Caba Sánchez Laura Cecilia
1
, Soto Eguibar Enrique
1
, Vega Y Saenz de Miera Maria del
Rosario
1
,
Félix Grijalva Ricardo
2
.
1
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México.
2
Departamento de Biología Celular, Centro de Investigación y Estudios Avanzado del Instituto
Politécnico Nacional (CINVESTAV-IPN), CDMX, México
Acid Sensing Ion Channels (ASIC) are proton-activated Na+ channels expressed in the nervous
system, where they are involved in learning, fear behavior, neurodegeneration, nociception,
mechanoreception, chemoreception, ischemia, epilepsy, inflammation, among others. Thus, the
discovery of pharmacological agents targeting ASICs has high therapeutic potential.
Minocycline is a semisynthetic antibiotic of the tetracycline family that has neuroprotective
properties, in processes in which ASICs have been involved (such as neurodegeneration,
nociception, and inflammation), which led us to postulate the ASICs as a minocycline target. As
we hypothesized, whole cell voltage clamp recordings from isolated dorsal root ganglion (DRG)
neurons from the rat, shown that minocycline inhibits the peak amplitude of proton gated current
(ASIC) neurons in a dose-dependent manner (IC50 ~ 100 μM). In heterologous expression
system CHO-cells, minocycline selectively inhibits the ASIC1a currents without significant
inhibitory effects in ASIC2a, ASIC1b or ASIC3 currents. Molecular anchor analysis (in-silico
analyses) suggests the “acid pocket” and the “central vestibule” as putative minocycline bindings
sites in the chicken ASIC1a channel. These results demonstrate the inhibitory action of
minocycline on the ASIC currents, contributing to account for the neuroprotective action of
minocycline, and opening a venue for research of tetracycline derived molecules as potentially
relevant drugs to manipulate ASIC currents, and to improve neuroprotective therapeutic
armamentarium.