Aspartate Substitutions Establish the Concerted Action of P-region Glutamates in Repeats I and III in Forming the Protonation Site of L-type Ca2+ Channels

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Structured PICO

Population

L-type Ca2+ channels

Intervention

Glu --> Asp substitutions (EID, EIID, EIIID, EIVD) and Glu --> Ala substitution

Comparator

Wild-type channels

Outcome

Protonation affinity and H+ off-ratesurrogate

Multiple carboxylates (EI and EIII) work in concert to form a single high-affinity protonation site in L-type Ca2+ channels.

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Does not alter clinical Ca2+ channel management; leaves open whether EI/EIII coordination modulates proton sensitivity in mammalian models.

Chen et al. (1997) studied this question.

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Does not alter clinical Ca2+ channel management; leaves open whether EI/EIII coordination modulates proton sensitivity in mammalian models.