Molecular diversity and function of voltage-gated (Kv) potassium channels in epithelial cells

Voltage-gated K+ channels belonging to Kv1-9 subfamilies are widely expressed in excitable cells where they play an essential role in membrane hyperpolarization during an action potential and in the propagation of action potentials along the plasma membrane. Early patch clamp studies on epithelial cells revealed the presence of K+ currents with biophysical and pharmacologic properties characteristic of Kv channels expressed in excitable cells. More recently, molecular approaches including PCR and the availability of more selective antibodies directed against Kv alpha and auxiliary subunits, have demonstrated that epithelial cells from various organ systems, express a remarkable diversity Kv channel subunits. Unlike neurons and myocytes however, epithelial cells do not typically generate action potentials or exhibit dynamic changes in membrane potential necessary for activation of Kv alpha subunits. Moreover, the fact that many Kv channels expressed in epithelial cells exhibit inactivation suggest that their activities are relatively transient, making it difficult to ascribe a functional role for these channels in transepithelial electrolyte or nutrient transport. Other proposed functions have included (i) cell migration and wound healing, (ii) cell proliferation and cancer, (iii) apoptosis and (iv) O2 sensing. Certain Kv channels, particularly Kv1 and Kv2 subfamily members, have been shown to be involved in the proliferation of prostate, colon, lung and breast carcinomas. In some instances, a significant increase in Kv channel expression has been correlated with tumorogenesis suggesting the possibility of using these proteins as markers for transformation and perhaps reducing the rate of tumor growth by selectively inhibiting their functional activity.