The non-selective voltage-activated cation channel in the human red blood cell membrane: reconciliation between two conflicting reports and further characterisation

Using the patch-clamp technique, the non-selective, voltage-activated cation channel in the human red blood cell (RBC) membrane was further characterised. Activity of the cation channel could be demonstrated at a range of salt concentrations with the current–voltage characteristics for monovalent cations going from linear to superlinear functions, depending on the cation concentration in the range of 100–500 mM. The non-selective voltage-activated cation channel was demonstrated to be permeable to the divalent cations Ca2+ and Ba2+, and even Mg2+. The current–voltage relations for the divalent cations were superlinear even at 75 mM salt concentration, but indicated outward rectification in contrast to the I–V curve for monovalent cations. The degree of activation at a given membrane potential depended strongly on the prehistory of the channel. The gating exhibited hysteretic-like behaviour, since the quasi steady-state deactivation and activation curves were displaced by ∼25 mV. This result fully explains apparent discrepancies between V0.5-values previously obtained by slightly different experimental protocols. The possible physiological/pathophysiological role of the channel is discussed in the context of the demonstrated permeability for divalent cations.