Gβγ Binding to GIRK4 Subunit Is Critical for G Protein-gated K+ Channel Activation

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Structured PICO

Population

Native purified IKACh, peptides derived from GIRK1 or GIRK4 amino acid sequences, and mutated subunits expressed in mammalian cells

Intervention

Mutational analysis of GIRK4 (C216T point mutation and 5 amino acid conversion in region 226-245)

Comparator

Wild-type GIRK4 / unmutated IKACh channels

Outcome

Gbeta gamma binding to IKACh and Gbeta gamma activation of expressed channelssurrogate

Gbeta gamma binding to the GIRK4 subunit is critical for the activation of the cardiac G protein-gated K+ channel (IKACh).

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Demonstrates GIRK4-Gβγ binding is essential for IKACh activation; leaves open whether this domain is a viable therapeutic target.

Krapivinsky et al. (1998) studied this question.

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