Key result
siRNA-mediated knockdown of LRRC8A accelerated the inactivation of VSOR currents but did not affect ASOR currents, indicating distinct molecular contributions to these anion channels.
p-value: p=<0.05
LRRC8A is associated with the deceleration mechanism of VSOR inactivation, whereas ASOR activity is independent of LRRC8 family members.
LRRC8A selectively modulates VSOR inactivation in animal cells; leaves open cardiovascular roles and therapeutic targeting.
Volume- and acid-sensitive outwardly rectifying anion channels (VSOR and ASOR) activated by swelling and acidification exhibit voltage-dependent inactivation and activation time courses, respectively. Recently, LRRC8A and some paralogs were shown to be essentially involved in the activity and inactivation kinetics of VSOR currents in human colonic HCT116 cells. In human cervix HeLa cells, here, inactivation of VSOR currents was found to become accelerated by RNA silencing only of LRRC8A but never decelerated by that of any LRRC8 isoform. These data suggest that LRRC8A is associated with the deceleration mechanism of VSOR inactivation, while none of LRRC8 members is related to the acceleration mechanism. Activation kinetics of ASOR currents was unaffected by knockdown of any LRRC8 family member. Double, triple and quadruple gene-silencing studies indicated that combinatory expression of LRRC8A with LRRC8D and LRRC8C is essential for VSOR activity, whereas none of LRRC8 family members is involved in ASOR activity.
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Sato et al. (2016) studied Cervical cancer (HeLa cells). siRNA-mediated knockdown of LRRC8A vs. Non-targeting siRNA was evaluated on Apparent half-inactivation time of VSOR currents (p=<0.05). siRNA-mediated knockdown of LRRC8A accelerated the inactivation of VSOR currents but did not affect ASOR currents, indicating distinct molecular contributions to these anion channels.
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