Effects of Fe(2+) on ion channels: Na(+) channel, delayed rectified and transient outward K(+) channels.
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 microM Fe(2+), respectively. Differences between two groups were significant (P<0.05, n=12-15), except for that between the control and 1 microM (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 microM 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 microM 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.
Ge
S Y
SY
School of Life Science, University of Science and Technology of China, 230027, Hefei Anhui, PR China.
Ruan
D Y
DY
Yu
K
K
Chen
J T
JT
Wang
M
M
Zhong
G S
GS
D000818:Animals; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels; D007501:Iron / Q000494:pharmacology* / Q000502:physiology; D008564:Membrane Potentials; D009424:Nervous System Physiological Phenomena / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology
D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D007501:Iron