Dendrotoxin: a selective blocker of a non-inactivating potassium current in guinea-pig dorsal root ganglion neurones

Pflugers Arch. 1986 Oct;407(4):365-9. doi: 10.1007/BF00652619.

Abstract

The voltage clamp technique was used to study the effects of dendrotoxin (DTX) on outward potassium currents in internally perfused dorsal root ganglion neurones of guinea-pig. Sodium currents were eliminated by tetrodotoxin (TTX, 2 mumol/l), calcium currents and calcium-activated potassium conductances were abolished by intracellular perfusion of cells with KF. Depolarizing voltage shifts from a holding potential of -90 mV yielded a fast transient outward current (IfK) and a delayed non-inactivating outward current (IsK). These currents could be separated by shifting the membrane potential to -50 mV, where IfK was almost completely inactivated. DTX, at concentrations of 0.14-1.4 nmol/l selectively reduced a portion of the non-inactivating potassium current, leaving the transient outward current unaffected. Once manifested, the action of DTX could not be reversed by washing. The I-V characteristic of the current blocked by DTX is almost linear and quite different from the one of the 'DTX-resistant' portion of IsK, which shows a non-linear I-V curve. Tetraethylammonium (TEA, 30 mmol/l) strongly reduced IfK and IsK. However, subsequent application of DTX was still able to further reduce IsK. 3,4-diaminopyridine (3,4-DAP, 500 mumol/l) unselectively reduced IfK and a portion of IsK. The remainder of the latter could not further be reduced by DTX, suggesting a similar action of the two blockers on non-inactivating potassium currents. From the results presented, it is suggested that dendrotoxin selectively blocks a non-inactivating subtype of potassium channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine* / analogs & derivatives*
  • Amifampridine
  • Aminopyridines / pharmacology
  • Animals
  • Elapid Venoms / antagonists & inhibitors
  • Elapid Venoms / pharmacology*
  • Ganglia, Spinal / drug effects*
  • Guinea Pigs
  • In Vitro Techniques
  • Ion Channels / drug effects*
  • Membrane Potentials / drug effects
  • Potassium / metabolism*
  • Tetraethylammonium
  • Tetraethylammonium Compounds / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • Aminopyridines
  • Elapid Venoms
  • Ion Channels
  • Tetraethylammonium Compounds
  • Tetrodotoxin
  • Tetraethylammonium
  • dendrotoxin
  • 4-Aminopyridine
  • Amifampridine
  • Potassium