Transfection And Stable Expression Of Voltage-gated Potassium Channels And Its Pathology And Pharmacology In Alzheimer's Disease Model

Part I Electrophsiological property correspondence between Kv4.2, Kv4.3 currents and A-type potassium current in the cultured rat hippocampal neuronA-type potassium current has been found in a wide variety of mammalian neuron, which characterized by rapid activation and inactivation. A-type potassium channel are important in modulation of action potential configuration and neuronal firing patterns. Alterations in the amplitude or kinetics of I_A may impact on the shape and duration of action potential. Recently, A-type potassium current has been recorded from the somatodendritic of hippocampal neurons, which play an important role in pre- and postsynaptic neuronal excitation. Since I_A plays key role in dendritic excitability of hippocampal neurons, it may have an influence in the long-term potentiation, the fundamental phenomenon of learning and memory. To further determined the molecular structure of Ia, we observed the electrophysiological properties of Kv4.2, Kv4.3 expressed in mammalian cell in comparison to native I_A in the hippocampal neurons by transfection, primary cultured rat hippocampus neurons and whole cell voltage clamp techniques. The results showed that the expressed Kv4.2, Kv4.3 current and cultured hippocampus neurons transient outward current both display "A"-like current properties. The time constant of decay in cultured rat hippocampal neurons and Kv4.2, Kv4.3 currents were 42.3 ± 10.9 ms (I_A), 26.3 ± 14.5 ms (Kv4.2) and 99.3 ± 36.0 ms (Kv4.3), respectively. The activation curve of I_A current in the cultured rat hippocampal neurons and Kv4.2, Kv4.3 currents were better fitted by simple Boltzmann function with V_1/2-7.2 + 5.3 mV, K 25.2 + 5.0 mV for I_A, and V_1/2-7.2± 3.8 mV, K 19.3±6.0 mV for Kv4.2, V_1/2 -7.8 + 5.1 mV, K 17.3±2.6 mV for Kv4.3, respectively. The steady -state inactivation curves showed that the voltage for half maximal inactivation and the slope factor (k) were -70.6 ±14.3 mV, 9.7 + 5.1 mV in IA, -67.6 ± 7.4 mV, 6.2±2.3 mV in Kv4.2 and -46.5±8.8 mV, 7.5±3.0 mV for Kv4.3 currents, respectively. Comparison of the recovery from inactivation of these potassium currents, the time constants of recovery for Kv4.2 and Kv4.3 currents were significant slower than that of I_A in hippocampal neuron. The time constants (t) were of 55.2 ± 16.8 ms, 200.1±51.5 ms and 240.2± 122.1 ms for I_A and Kv4.2, Kv4.3 currents, respectively. These results suggested that Kv4.2 is a major component of I_A...