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.
Lüthi
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A
Yale University School of Medicine, Section of Neurobiology, New Haven, Connecticut 06510, USA.
McCormick
D A
DA
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