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The MinK-related peptides
Zoe A McCrossan1, Geoffrey W Abbott
1Greenberg Division of Cardiology, Department of Medicine, Department of Pharmacology, Weill Medical College of Cornell University, Starr 463, 520 East 70th Street, New York, NY 10021, USA.
Abstract:
Voltage-gated potassium (Kv) channels mediate rapid, selective diffusion of K+ ions through the plasma membrane, controlling cell excitability, secretion and signal transduction. KCNE genes encode a family of single transmembrane domain proteins called MinK-related peptides (MiRPs) that function as ancillary or beta subunits of Kv channels. When co-expressed in heterologous systems, MiRPs confer changes in Kv channel conductance, gating kinetics and pharmacology, and are fundamental to recapitulation of the properties of some native currents. Inherited mutations in KCNE genes are associated with diseases of cardiac and skeletal muscle, and the inner ear. This article reviews our current understanding of MiRPs--their functional roles, the mechanisms underlying their association with Kv alpha subunits, their patterns of native expression and emerging evidence of the potential roles of MiRPs in the brain. The ubiquity of MiRP expression and their promiscuous association with Kv alpha subunits suggest a prominent role for MiRPs in channel dependent systems.
Insights
MinK-related peptides (MiRPs) are crucial beta subunits for voltage-gated potassium (Kv) channels, influencing their function and associated diseases. Their widespread expression suggests significant roles in cellular signaling and the brain.
Area of Science:
- Molecular Biology
- Neuroscience
- Cardiology
Background:
- Voltage-gated potassium (Kv) channels regulate essential cellular functions like excitability and signal transduction.
- KCNE genes encode MinK-related peptides (MiRPs), which act as beta subunits modulating Kv channel properties.
Purpose of the Study:
- To review the functional roles and mechanisms of MiRPs in Kv channel regulation.
- To explore the native expression patterns and emerging roles of MiRPs in the brain.
Main Methods:
- Review of existing literature on KCNE genes, MiRPs, and Kv channel interactions.
- Analysis of functional studies demonstrating MiRPs' impact on Kv channel conductance, gating, and pharmacology.
- Examination of genetic studies linking KCNE mutations to human diseases.
Main Results:
- MiRPs significantly alter Kv channel biophysical and pharmacological properties when co-expressed.
- Mutations in KCNE genes are implicated in cardiac, skeletal muscle, and inner ear disorders.
- Evidence suggests MiRPs are widely expressed and interact with various Kv alpha subunits.
Conclusions:
- MiRPs are fundamental to the function of specific Kv channels and the pathophysiology of related diseases.
- The promiscuous association of MiRPs with Kv alpha subunits indicates a broad physiological importance.
- Emerging data highlight potential critical roles for MiRPs in neurological systems.
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