Differential sensitivity of amphibian nodal and paranodal K+ channels to 4-aminopyridine and TEA.
Voltage-dependent K+ channels are blocked by several drugs, including 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP is most widely used to localize K+ channels in mammalian and non-mammalian nerve fibers, but 4-AP and TEA alter various K+ channels and/or preparations in specific ways. The reason is not known, in part because dissociation constants for 4-AP and TEA have not been measured for nodal and internodal K+ channels in the same fibers. Smith and Schauf showed that the density of nodal versus paranodal K+ channels in frog nerves depends on fiber diameter. The size dependence was used to determine the relative sensitivity of nodal and internodal K+ channels to 4-AP and TEA, and to compare voltage- and time-dependent activation. The results show nodal and internodal K+ channels activate similarly. However, internodal channels are selectivity blocked by 4-AP while TEA is more effective on nodal channels. A high sensitivity of internodal K+ channels may explain why 4-AP improves symptoms in diseases such as multiple sclerosis.
D015761:4-Aminopyridine; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009412:Nerve Fibers / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D011894:Rana pipiens / Q000502:physiology*; D011901:Ranvier's Nodes / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D000631:Aminopyridines; D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D019789:Tetraethylammonium; D012964:Sodium; D015761:4-Aminopyridine; D011188:Potassium