Effects of Fe2+ on ion channels: Na+ channel, delayed rectified and transient outward K+ channels

The effects of Fe2+ on the properties of three types of ion channels were studied in acutely dissociated rat hippocampal pyramidal neurons from area CA1 at postnatal ages of 7–14 days using the whole cell patch clamp technique. The results indicated that: (1) in the existence of Fe2+, the activation voltage threshold of transient outward K+ currents (IA) was decreased. The normalized current-voltage curves of activation were well fitted with a single Boltzmann function, and the V1/2 was 2.44±1.14 mV (n=15) in control, whereas 1.79±1.53 (n=15), −2.96±0.92 (n=14), −5.11±1.31 (n=13), −9.05±1.64 mV (n=12) in 1, 10, 100 and 1000 μm Fe2+, respectively. Differences between two groups were significant (P<0.05, n=12–15), except for that between the control and 1 μm (P>0.05, n=15). (2) Fe2+ caused a left shift of the current–voltage curves of steady-state inactivation of IA in a concentration-dependent manner. The curves were well fitted with a single Boltzmann function with similar slope (P>0.05, n=10–13). The V1/2 were −70.71±1.23 (n=13), −71.14±1.37 (n=13), −78.21±1.17 (n=11), −84.61±1.34 (n=12), and −89.68±2.59 mV (n=10) in control, 1, 10, 100 and 1000 μm Fe2+, respectively. Fe2+ also shifted the current–voltage curves of Na+ channel steady-state inactivation to more negative depolarization potentials in parallel, with V1/2, −67.37±1.33 mV (n=12) in control, and −67.52±1.28 mV (n=12), −68.24±1.61 mV (n=10), −71.58±1.45 mV (n=10), −76.65±1.76 mV (n=9) in 1, 10, 100 and 1000 μm Fe2+ solutions, respectively. (3) In Fe2+ solutions, the recovery from inactivation of IA was slowed. (4) With application of different concentrations of Fe2+, the voltage threshold of activation of delayed rectified outward K+ currents (IK) was decreased, while Fe2+ showed a little inhibition at more positive depolarization. Briefly, the results demonstrated that Fe2+ is a dose- and voltage-dependent, reversible modulator of IA, IK and Na+ channels. The results will be helpful to explain the mechanism of Fe2+ physiological function and Fe2+ intoxication in the central nervous system.