Effects of Fe 2+ on ion channels: Na + channel, delayed rectified and transient outward K + channels

Abstract

The effects of Fe 2+ 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 Fe 2+, the activation voltage threshold of transient outward K + currents (I A) was decreased. The normalized current-voltage curves of activation were well fitted with a single Boltzmann function, and the V 1/2 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 μ m Fe 2+, respectively. Differences between two groups were significant ( P<0.05, n=12–15), except for that between the control and 1 μ m ( P>0.05, n=15). (2) Fe 2+ caused a left shift of the current–voltage curves of steady-state inactivation of I A 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 V 1/2 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 μ m Fe 2+, respectively. Fe 2+ also shifted the current–voltage curves of Na + channel steady-state inactivation to more negative depolarization potentials in parallel, with V 1/2, −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 μ m Fe 2+ solutions, respectively. (3) In Fe 2+ solutions, the recovery from inactivation of I A was slowed. (4) With application of different concentrations of Fe 2+, the voltage threshold of activation of delayed rectified outward K + currents (I K) was decreased, while Fe 2+ showed a little inhibition at more positive depolarization. Briefly, the results demonstrated that Fe 2+ is a dose- and voltage-dependent, reversible modulator of I A, I K and Na + channels. The results will be helpful to explain the mechanism of Fe 2+ physiological function and Fe 2+ intoxication in the central nervous system.