The classical direct effects of nuclear receptors on gene regulation normally take hours before a functional effect is seen in cells because of the large number of intermediate steps between nuclear receptor activation and changes in protein expression levels. However it has been observed that many effects of the application of nuclear hormones, such as changes in ion channel activity, occur within minutes which is inconsistent with the classical mechanism of nuclear receptor action. While the molecular target for these non-genomic effects of nuclear receptors has not been conclusively demonstrated, it has been hypothesized that there are variants of nuclear receptors which are membrane associated instead of being localized in the cytosol or nucleus. Furthermore, these membrane associated receptors function through alternative signal transduction mechanisms not involving gene regulation.