Interaction of 4-aminopyridine with normal and chloramine-T-modified K channels of neuroblastoma cells.
The steady-state effects and rate of action of 4-aminopyridine (4-AP) on normal and chloramine-T (CL-T)-modified voltage-dependent potassium (K) currents were studied in neuroblastoma cells with the whole-cell voltage-clamp current recording technique. 4-AP apparently slows both the activation and inactivation of the normal current but does not modify the time course of the CL-T-modified current. These differential effects of 4-AP are interpreted as resulting from the existence of two types of K channels with different 4-AP sensitivities under normal conditions and similar 4-AP sensitivities after CL-T, which furthermore slows their inactivation [8, 9]. While the onset of 4-AP action on the normal current is delayed and can be described by the difference of two exponentials, the onset of 4-AP action on CL-T-modified current starts immediately after the external application of the drug and can be described by the sum of two exponentials. The 4-AP-induced block of the normal current exhibits use-dependent features and is relieved by long conditioning depolarizations. In contrast, the block of the CL-T-modified current is not use-dependent. At high 4-AP concentrations (1-10 mM), the steady-state block of the normal current reaches a saturating value of 95%, while the steady-state block of the CL-T-modified current and the "unblocked" normal current only reaches a saturating value of 35%. The results suggest that CL-T inhibits a channel or membrane constituent which contributes to the inactivation of channels and increases their apparent affinity for 4-AP when they are in closed or open states.(ABSTRACT TRUNCATED AT 250 WORDS)
Dubois
J M
JM
Laboratoire de Physiologie Comparée, URA CNRS 1121, Orsay, France.
Rouzaire-Dubois
B
B
D015761:4-Aminopyridine / Q000494:pharmacology*; D002700:Chloramines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014105:Tosyl Compounds; D014407:Tumor Cells, Cultured
D002700:Chloramines; D015221:Potassium Channels; D014105:Tosyl Compounds; C016300:chloramine-T; D015761:4-Aminopyridine