Block by 4‐aminopyridine of a Kv1.2 delayed rectifier K+ current expressed in Xenopus oocytes.

Abstract

1. The blocking action of 4-aminopyridine (4-AP) on a delayed rectifier K,12 K+ channel expressed in oocytes was investigated at room temperature (22°C) and physiological temperature (34°C) using the double-electrode voltage clamp and patch clamp techniques. 2. At room temperature, 4-AP (100 uM) inhibition occurred only after activation of current. The rate of onset of block was dependent upon the length of time current was activated by a depolarizing step. Similarly, removal of block required current activation. The degree of steady-state block by 4-AP was not reduced by increasingly more depolarized step potentials. The degree of steady-state block also did not change over the duration of a I s step.3. When channels were nearly fully inactivated, 4-AP produced no additional block of a subsequent depolarizing step, suggesting that 4-AP did not bind when channels were in the inactivated state. In single channel experiments, 4-AP decreased the mean open time in a dose-dependent manner but did not alter the single-channel current amplitude. 4. At 34°C the I-V relationship and inactivation curve shifted to more negative potentials. Increasing the temperature to 34°C did not alter the degree of block by 4-AP, although the rate of onset of block was greatly enhanced.

Kv1.2-Containing K+Channels Regulate Subthreshold Excitability of Striatal Medium Spiny Neurons

“…The response of the model to standard step activation and inactivation protocols is shown in Fig. 6, E and F. Both sets of data resemble experimentally generated currents in medium spiny neurons as well as currents in heterologous systems expressing Kv1.2 channels (Coetzee et al 1999;Russell et al 1994;Sprunger et al 1996). So, although not perfect, the model captures key features of the Kv1.2 channel currents seen in medium spiny neurons, making it suitable to use as a tool to explore how these channels might contribute to spike generation and repetitive activity.…”

“…In addition to ␣-DTX, Kv1.2 channels are readily blocked by 4-aminopyridine (4-AP) at micromolar concentrations (Russell et al 1994). Application of 100 M 4-AP reduced currents evoked by the slow voltage ramp by approximately the same amount as did ␣-DTX.…”

Inactivation of Voltage-Gated Cardiac K + Channels

“…Block by 4-AP is an important case in point. Although it acts from an intracellular and not an extracellular site, 47,49,[85][86][87] it clearly competes with, rather than increases, C-type inactivation in Kv1.1 47 and Kv1.2 49 channels. 4-AP also competes with development of C-type inactivation of Shaker K ϩ channels from an intracellular site.…”

Heteromultimeric Kv1.2-Kv1.5 Channels Underlie 4-Aminopyridine-Sensitive Delayed Rectifier K + Current of Rabbit Vascular Myocytes

“…10 -12 Previous studies show considerable variability in the state-dependence of 4-AP block, eg, during or after activation (open-state block), closed (resting)-state block, or block after inactivation. [12][13][14][15][16] Identification of the mechanism(s) of 4-AP block has been advanced through the study of recombinant Kv channels. For example, analyses of the effects of 4-AP on Shaker family Kv1 channels, including Kv1.2, Kv1.4 and Kv1.5, 14,16 -20 as well as Kv2.1 and Kv3.…”