Key result
Beta-adrenergic stimulants enhance cardiac L-type Ca2+ current via cyclic AMP-mediated channel phosphorylation.
Why the study?
The mechanism by which beta-adrenergic stimulants enhance cardiac L-type Ca2+ channel current through phosphorylation and gating modulation was investigated.
This study elucidates the single-channel gating mechanisms by which beta-adrenergic stimulation enhances cardiac L-type calcium currents via cAMP-dependent phosphorylation.
Beta-adrenergic effects on L-type Ca channel availability support mechanistic studies; leaves open translation to human arrhythmia or HF models.
The cardiac L-type Ca2+ channel current is enhanced by beta-adrenergic stimulants by phosphorylation mediated by an increase in cyclic AMP. Single-channel studies have revealed that the Ca2+ channels are not always allowed to open at test steps from large negative holding potentials and beta-agonists increase the ratio of current-containing sweeps (availability, Ps). The duration of available (Ts) and unavailable states (TF) are measurable by applying a large number of test pulses. beta-Agonists shorten TF and prolong TS, possibly by enhancing channel phosphorylation by activating cyclic AMP-dependent protein kinase and by inhibiting channel dephosphorylation by phosphorylating phosphatase inhibitor 1, respectively, if the available state reflects the phosphorylated state of the channel. The modulation of the slow gating process, the increase in PS, plays a primary role in increasing the L-type Ca2+ current at moderate increase in sympathetic activity. When a larger increase in cyclic AMP is resulted, moduration of burst-kinetics including mode 2 openings also produced by phosphorylation enhances further the Ca2+ current.
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Rikuo Ochi (1993) conducted a review in Cardiac L-type Ca2+ channel current enhancement. Beta-adrenergic stimulants was evaluated on Cardiac L-type Ca2+ channel current enhancement. Beta-adrenergic stimulants enhance cardiac L-type Ca2+ current by increasing cyclic AMP, which modulates slow gating processes and burst-kinetics via channel phosphorylation.
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