The effects of 4-aminopyridine (4-AP) on the delayed K+ current and on the Ca2+-activated K+ current of the Aplysia pacemaker neurons R-15 and L-6 were studied. The delayed outward K+ current was measured in Ca2+-free artificial seawater (ASW) containing tetrodotoxin (TTX), using brief depolarizing clamp pulses. External (and internal) 4-AP blocks the delayed K+ current in a dose-dependent manner but does not block the leakage current. Our results show that one 4-AP molecule combines with a single receptor site and that the block is voltage dependent with an apparent dissociation constant (K4-AP) of approximately 0.8 mM at 0 mV. K4-AP increases e-fold for a 32-mV change in potential, which is consistent with the block occurring approximately 0.8 of the distance through the membrane electrical field. The 4-AP block appears to depend upon stimulus frequency as well as upon voltage. The greater speed of onset of the block produced by internal 4-AP relative to when it is used externally suggests that 4-AP acts from inside the cell. The Ca2+-activated K+ current was measured in Ca2+-free ASW containing TTX, using internal Ca2+-ion injection to directly activate the K+ conductance. Low external 4-AP concentrations (less than 2 mM) have no effect on the Ca2+-activated K+ current, but concentrations of 5 mM or greater increase the K+ current. Internal 4-AP has the same effect. The opposing effects of 4-AP on the two components of the K+ current can be seen in measurements of the total outward K+ current at different membrane potentials in normal ASW and during the repolarizing phase of the action potential.
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1 July 1981
Article|
July 01 1981
Effects of 4-aminopyridine on potassium currents in a molluscan neuron.
A Hermann
A L Gorman
Online ISSN: 1540-7748
Print ISSN: 0022-1295
J Gen Physiol (1981) 78 (1): 63–86.
Citation
A Hermann, A L Gorman; Effects of 4-aminopyridine on potassium currents in a molluscan neuron.. J Gen Physiol 1 July 1981; 78 (1): 63–86. doi: https://doi.org/10.1085/jgp.78.1.63
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