Modulation of a pacemaker current through Ca(2+)-induced stimulation of cAMP production.
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.
Yale University School of Medicine, Section of Neurobiology, New Haven, Connecticut 06510, USA.
A
A
Lüthi
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DA
McCormick
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002147:Calmodulin / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism*; D005289:Ferrets; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010782:Photolysis; D013788:Thalamus / Q000502:physiology*
D002147:Calmodulin; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D002118:Calcium