Increased calcium-dependent K+ channel activity contributes to the maturation of cellular firing patterns in developing cerebellar Purkinje neurons.
Developmental changes in neuronal excitability reflect the regulated expression of ion channels and receptors. Purkinje neurons of the rat cerebellum progress from slow irregular firing to a fast pacemaker-like pattern during postnatal development in vivo. In this study, a comparable period of development in culture was investigated at the protein level using cell-attached single channel recordings to quantify the abundance of active calcium-dependent (KCa) and delayed rectifier (KD) potassium channels. In control cultures, KCa channel activity increased whereas KD channel activity was not significantly different with developmental age. The increase in active KCa channels was antagonized by chronic treatment with the blocker, tetraethylammonium (TEA, 1 mM), which also retarded the normal development of cellular firing patterns. The consequences of chronic TEA treatment were assessed in cultures after thorough washout of the TEA-containing culture medium. Current clamp analyses (nystatin-perforated patches) showed that control Purkinje neurons progressed from a single spike mode to a repetitive firing mode, with a concomitant decrease in action potential duration and an increase in maximal firing rate. Chronic TEA treatment prevented these changes; Purkinje neurons retained the slow firing rate and long duration action potentials that are typical of the immature state. These data suggest that the developmental increase in KCa channel activity may be required for the maturation of cellular firing patterns in cerebellar Purkinje neurons.
Department of Physiology, University of Arizona, Tucson 85724-5051, USA.
Y L
YL
Muller
A J
AJ
Yool
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D051668:Delayed Rectifier Potassium Channels; D005260:Female; D005333:Fetus / Q000166:cytology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011247:Pregnancy; D011689:Purkinje Cells / Q000737:chemistry* / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology
D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015222:Sodium Channels; D019789:Tetraethylammonium; D002118:Calcium