Abstract

The epithelial Na + channel (ENaC) is composed of the subunits α, β, and γ [Canessa et al., Nature 367 (1994) 463–467] and typically exhibits a high affinity to amiloride [Canessa et al., Nature 361 (1993) 467–470]. When expressed in Xenopus oocytes, conflicting results were reported concerning the osmo-sensitivity of the channel [Ji et al., Am. J. Physiol. 275 (1998) C1182–C1190; Hawayda and Subramanyam, J. Gen. Physiol. 112 (1998) 97–111; Rossier, J. Gen. Physiol. 112 (1998) 95–96]. Rat hepatocytes were the first system in which amiloride-sensitive sodium currents in response to hypertonic stress were reported [Wehner et al., J. Gen. Physiol. 105 (1995) 507–535; Wehner et al., Physiologist 40 (1997) A-4]. Moreover, all three ENaC subunits are expressed in these cells [Böhmer et al., Cell. Physiol. Biochem. 10 (2000) 187–194]. Here, we injected specific antisense oligonucleotides directed against α-rENaC into single rat hepatocytes in confluent primary culture and found an inhibition of hypertonicity-induced Na + currents by 70%. This is the first direct evidence for a role of the ENaC in cell volume regulation.

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