Temporal synaptic tagging by I(h) activation and actin: involvement in long-term facilitation and cAMP-induced synaptic enhancement.

Presynaptic I(h) channels become activated during a tetanus through membrane hyperpolarization resulting from Na(+) accumulation and electrogenic Na(+)/K(+) exchange. I(h) activation is obligatory for inducing long-term facilitation (LTF), a long-lasting synaptic strengthening. cAMP-induced synaptic enhancement also requires I(h) activation, and both processes are sensitive to actin depolymerization. Other mechanisms are responsible for expression of the responses. Once initiated, continued response to cAMP is I(h) and actin independent. Moreover, LTF-induced activation of I(h) renders subsequent cAMP enhancement insensitive to both I(h) blockers and actin depolymerization. This actin-stabilized "temporal synaptic tagging" set by I(h) activation is prolonged when I(h) is activated concurrent with an elevation in presynaptic calcium concentration ([Ca(2+)]i), permitting the further strengthening of synapses given appropriate additional stimuli.