Ca(2+)-dependent activation of T-type Ca2+ channels by calmodulin-dependent protein kinase II

Am J Physiol. 1994 Jul;267(1 Pt 2):F183-9. doi: 10.1152/ajprenal.1994.267.1.F183.

Abstract

The T-type Ca2+ channel is unique among voltage-dependent Ca2+ channels in its low threshold for opening and its slow kinetics of deactivation. Here, we evaluate the importance of intracellular Ca2+ (Cai2+) in promoting low-threshold gating of T-type channels in adrenal glomerulosa cells. We observe that 390 nM to 1.27 microM Cai2+ enhances T-type current by shifting the voltage dependence of channel activation to more negative potentials. This Ca(2+)-induced shift is mediated by calmodulin-dependent protein kinase II (CaMKII), because it is abolished by inhibitors of CaMKII but not of protein kinase C and is subsequently restored by exogenous calmodulin. This Ca(2+)-induced reduction in gating threshold would render T-type Ca2+ channels uniquely suited to transduce depolarizing stimuli of low amplitude into a Ca2+ signal sufficient to support a physiological response.

Publication types

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

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine* / analogs & derivatives*
  • Animals
  • Calcium / pharmacology*
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / pharmacology*
  • Cattle
  • Electrophysiology
  • Isoquinolines / pharmacology
  • Piperazines / pharmacology
  • Zona Glomerulosa / cytology
  • Zona Glomerulosa / metabolism
  • Zona Glomerulosa / physiology

Substances

  • Calcium Channels
  • Isoquinolines
  • Piperazines
  • KN 62
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium