Thapsigargin Inhibits a Potassium Conductance and Stimulates Calcium Influx in the Intact Rat Lens

J Physiol. 1999 Apr 1;516 ( Pt 1)(Pt 1):191-9. doi: 10.1111/j.1469-7793.1999.191ab.x.

Abstract

1. An increase in lens cell calcium has long been associated with cortical cataract. Recently, it has been shown that thapsigargin induces a rise in lens cell calcium by release from endoplasmic reticulum stores. The effects of this rise on the optical and membrane characteristics of the lens were studied in the isolated rat lens. 2. The electrical characteristics of the isolated, perifused rat lens were measured using a two-internal microelectrode technique that permits measurement of plasma membrane conductance (Gm), membrane potential (Vm) and junctional conductance in the intact lens. 3. Thapsigargin (1 microM) induced a rapid overall depolarization of Vm that was accompanied by first a decrease and then an increase in Gm. 4. Replacing external Na+ with tetraethylammonium (TEA) abolished the decrease in Gm. However, a transient increase phase was still observed. 5. The changes in conductance were further characterized by measuring 22Na+ and 45Ca2+ influxes into the isolated lens. Thapsigargin (1 microM) induced a transient increase in 45Ca2+, but did not affect Na+ influx. 6. The Ca2+ channel blocker La3+ (10 microM) totally inhibited the thapsigargin-induced Ca2+ influx. It also blocked the increase in Gm observed in control and in Na+-free-TEA medium. In the absence of external calcium, thapsigargin induced a small depolarization in Vm. 7. These data indicate that thapsigargin induces both a decrease in K+ conductance and an increase in Ca2+ conductance. These probably result from release of stored Ca2+ and subsequent activation of store-operated Ca2+ channels (capacitative Ca2+ entry). 8. Thapsigargin application over the time course of these experiments (24 h) had no effect on junctional conductance or on the transparency of the lens.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Electrophysiology
  • Enzyme Inhibitors / pharmacology*
  • In Vitro Techniques
  • Kinetics
  • Lanthanum / pharmacology
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / metabolism*
  • Lens, Crystalline / physiology
  • Membrane Potentials / physiology
  • Microelectrodes
  • Neural Conduction / drug effects
  • Patch-Clamp Techniques
  • Potassium Channel Blockers*
  • Rats
  • Sodium / metabolism
  • Tetraethylammonium / pharmacology
  • Thapsigargin / pharmacology*

Substances

  • Calcium Channel Blockers
  • Enzyme Inhibitors
  • Potassium Channel Blockers
  • Tetraethylammonium
  • Thapsigargin
  • Lanthanum
  • Sodium
  • Calcium