Non-stimulated Ca2+ leak pathway in cerebellar granule neurones

Biochem Pharmacol. 2005 Sep 1;70(5):786-93. doi: 10.1016/j.bcp.2005.06.004.

Abstract

The aim of this study was to investigate the pathways of calcium influx routes in non-stimulated cerebellar granule neurones by use of standard microspectrofluorimetric techniques. Repetitive application of Ca2+-free solutions for various time intervals induced decreases of resting cytosolic free Ca2+ concentration ([Ca2+]i) which were followed, on Ca2+ readmission, by a full recovery, always to the initial resting [Ca2+]i levels. Use of drugs to deplete calcium stores (thapsigargin, alone or combined with low levels of ionomycin) did not cause release of Ca2+ from the intracellular stores nor enhanced the activity of the Ca2+ entry pathway. This influx was mainly independent of voltage operated calcium channels, since both L-type channel blockers (nitrendipine) and the hyperpolarizing agent pinacidil (a K+-channel opener) were without effect. Contribution from glutamate receptors to this influx was eliminated since a combination of blockers of NMDA and AMPA glutamate receptors (NBQX and D-AP5) did not affect the properties of the Ca2+ response. The Ca2+ leak pathway was sensitive to micromolar levels of lanthanum and gadolinium, and to the compound 2-APB, features shared by several channels of the TRP superfamily. In summary, our results show the presence of a Ca2+ permeable pathway, active and patent in resting conditions in cerebellar granule neurones, and which is different from the voltage-operated calcium channels and not operated by depletion of the stores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / physiology
  • Cells, Cultured
  • Cerebellum / metabolism*
  • Lanthanoid Series Elements / pharmacology
  • Neurons / metabolism*
  • Rats
  • Thapsigargin / pharmacology

Substances

  • Calcium Channels
  • Lanthanoid Series Elements
  • Thapsigargin
  • Calcium