The role of dynamic palmitoylation in Ca2+ channel inactivation
AUTOR(ES)
Hurley, Joyce H.
FONTE
The National Academy of Sciences
RESUMO
N- and P/Q-type Ca2+ channels regulate a number of critical physiological processes including synaptic transmission and hormone secretion. These Ca2+ channels are multisubunit proteins, consisting of a pore-forming α1, and accessory β and α2δ subunits each encoded by multiple genes and splice variants. β subunits alter current amplitude and kinetics. The β2a subunit is associated with slowed inactivation, an effect that requires the palmitoylation of two N-terminal cysteine residues in β2a. In the current manuscript, we studied steady state inactivation properties of native N- and P/Q-type Ca2+ channels and recombinant N-type Ca2+ channels. When bovine α1B and β2a and human α2δ were coexpressed in tsA 201 cells, we observed significant variations in inactivation; some cells exhibited virtually no inactivation as the holding potential was altered whereas others exhibited significant inactivation. A similar variability in inactivation was observed in native channels from bovine chromaffin cells. In individual chromaffin cells, the amount of inactivation exhibited by N-type channels was correlated with the inactivation of P/Q-type channels, suggesting a shared mechanism. Our results with recombinant channels with known β subunit composition indicated that inactivation could be dynamically regulated, possibly by alterations in β subunit palmitoylation. Tunicamycin, which inhibits palmitoylation, increased steady-state inactivation of Ca2+ channels in chromaffin cells. Cerulenin, another drug that inhibits palmitoylation, also increased inactivation. Tunicamycin produced a similar effect on recombinant N-type Ca2+ channels containing β2a but not β2b or β2a subunits mutated to be palmitoylation deficient. Our results suggest that Ca2+ channels containing β2a subunits may be regulated by dynamic palmitoylation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=16861Documentos Relacionados
- An oily competition: role of β subunit palmitoylation for Ca2+ channel modulation by fatty acids
- Unique regulatory properties of the type 2a Ca2+ channel β subunit caused by palmitoylation
- Role of Ca2+ channel in cardiac excitation-contraction coupling in the rat: evidence from Ca2+ transients and contraction.
- Engineered calmodulins reveal the unexpected eminence of Ca2+ channel inactivation in controlling heart excitation
- Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and inactivation sites of skeletal muscle Ca2+ release channel.