Modulation of a pacemaker current through Ca(2+)-induced stimulation of cAMP production

Nat Neurosci. 1999 Jul;2(7):634-41. doi: 10.1038/10189.


Brief increases in [Ca2+]i can result in prolonged changes in neuronal properties. A Ca(2+)-dependent modulation of the hyperpolarization-activated cation current (Ih) controls the slow recurrence of synchronized thalamocortical activity. Here we show that the persistent activation of Ih is initiated by rapidly increased [Ca2+]i and subsequent production of cAMP. The modulation is maintained via a facilitated interaction of cAMP with open (voltage-gated) h-channels, inducing prolonged activation of Ih that may outlast the presence of increased free [Ca2+]i and [cAMP]i. This persistent Ih activation may control the presence and periodicity of both normal and abnormal synchronized thalamocortical rhythms.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Animals
  • Biological Clocks / physiology
  • Calcium / pharmacology
  • Calcium / physiology*
  • Calmodulin / pharmacology
  • Cerebral Cortex / physiology*
  • Cyclic AMP / metabolism*
  • Ferrets
  • Guanosine Triphosphate / pharmacology
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Neurons / drug effects
  • Neurons / physiology*
  • Photolysis
  • Thalamus / physiology*


  • Calmodulin
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Cyclic AMP
  • Calcium