Abstract

A developmental increase in delayed rectifier potassium current (I_Kv) in embryonicXenopus spinal neurons is critical for the maturation of excitability and action potential waveform. Identifying potassium channel genes that generate I_Kv is essential to understanding the mechanisms by which they are controlled. SeveralKv genes are upregulated during embryogenesis in parallel with increases in I_Kv and produce delayed rectifier current when heterologously expressed, indicating that they could encode channels underlying this current. We used antisense (AS) cRNA to test the contribution of xKv3.1to the maturation of I_Kv, becausexKv3.1 AS appears to suppress specifically heterologous expression of potassium current by xKv3.1 mRNA. The injection of xKv3.1 AS into embryos reduces endogenous levels of xKv3.1 mRNA in the developing spinal cord and reduces the amplitude and rate of activation ofI_Kv in 40% of cultured neurons, similar to the percentage of neurons in which endogenous xKv3.1transcripts are detected. The current in these mature neurons resembles that at an earlier stage of differentiation before the appearance ofxKv3.1 mRNA. Furthermore, AS expression increases the duration of the action potential in 40% of the neurons. No change in voltage-dependent calcium current is observed, suggesting that the decrease in I_Kv is sufficient to account for lengthening of the action potential. Computer-simulated action potentials incorporating observed reductions in amplitude and rate of activation of I_Kv exhibit an increase in duration similar to that observed experimentally. ThusxKv3.1 contributes to the maturation ofI_Kv in a substantial percentage of these developing spinal neurons.