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 (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 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 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 μM Fe²⁺, respectively. Fe²⁺ 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 μM Fe²⁺ solutions, respectively. (3) In Fe²⁺ solutions, the recovery from inactivation of I_A was slowed. (4) With application of different concentrations of Fe²⁺, the voltage threshold of activation of delayed rectified outward K⁺ currents (I_K) 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 I_A, I_K and Na⁺ channels. The results will be helpful to explain the mechanism of Fe²⁺ physiological function and Fe²⁺ intoxication in the central nervous system.