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 s tudied in acutely dissociated rat hippocampal pyramidal neurons from area C A1 at postnatal ages of 7-14 days using the whole cell patch clamp techniqu e. The results indicated that: (1) in the existence of Fe2+, the activation voltage threshold of transient outward K+ currents (I-A) was decreased. Th e normalized current-voltage curves of activation were well fitted with a s ingle Boltzmann function, and the V-1/2 was 2.44 +/-1.14 mV (n=15) in contr ol, 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 muM Fe2+, respectively. Di fferences between two groups were significant (P < 0.05, n=12-15), except f or that between the control and 1 muM (P > 0.05, n=15). (2) Fe2+ caused a l eft 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 si ngle Boltzmann function with similar slope (P > 0.05, n=10-13). The V-1/2 w ere -70.71 +/-1.23 (n=13), -71.14 +/-1.37 (n=13), -78.21 +/-1.17 (n=11), -8 4.61 +/-1.34 (n=12), and -89.68 +/-2.59 mV (n=10) in control, 1, 10, 100 an d 1000 muM Fe2+, respectively. Fe2+ also shifted the current-voltage curves of Na+ channel steady-state inactivation to more negative depolarization p otentials 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=1 0), -76.65 +/-1.76 mV (n=9) in 1, 10, 100 and 1000 muM Fe2+ solutions, resp ectively. (3) In Fe2+ solutions, the recovery from inactivation of I-A was slowed. (4) With application of different concentrations of Fe2+, the volta ge threshold of activation of delayed rectified outward K+ currents (I-K) w as decreased, while Fe2+ showed a little inhibition at more positive depola rization. Briefly, the results demonstrated that Fe2+ is a dose- and voltag e-dependent, reversible modulator of I-A, I-K and Na+ channels. The results will be helpful to explain the mechanism of Fe2+ physiological function an d Fe2+ intoxication in the central nervous system. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.