KQIEIKKFK

GAP19 Peptide (KQIEIKKFK) – Highly Specific Connexin43 Hemichannel Inhibitory Peptide

GAP19 (sequence KQIEIKKFK) is a selectively active Connexin43 (Cx43) mimetic peptide derived from the intracellular cytoplasmic loop (CL) domain of Cx43. Unlike broader connexin mimetics (e.g., Gap26 or Gap27), GAP19 uniquely inhibits Cx43 hemichannels without affecting gap-junctional intercellular communication (GJIC). This specificity has made GAP19 one of the most widely used research tools for dissecting Cx43-dependent signaling, inflammation, ischemia, and cell death mechanisms.

GAP19 has been validated in cardiac, neurological, vascular, and immune models, showing significant protective roles by preventing pathological hemichannel opening.

Molecular Details

• Sequence: KQIEIKKFK

• Length: 9 amino acids

• Origin: Derived from the L2 intracellular loop region of Connexin43

• Functional Domain: Inhibits Cx43 hemichannels by blocking the CT–CL interaction between the cytoplasmic loop and the C-terminal tail of Cx43.

• Selectivity:

  • Inhibits Cx43 hemichannels

  • Does not block Cx43 gap junction channels

  • Does not inhibit Cx40, Cx45, or pannexin channels

Functional Roles

GAP19 acts by preventing the cytoplasmic-loop (CL) and C-terminal (CT) domain interaction that regulates hemichannel gating. This leads to:Reduced ATP release; Reduced Ca²⁺ influx; Stabilization of membrane integrity; Suppression of inflammation and cell death signals; Protection during ischemia/reperfusion and excitotoxicity.

GAP19 is widely used as the gold-standard negative regulator of Cx43 hemichannel activity.

Applications in Research

1. Neuroprotection & Ischemic Brain Injury

GAP19 reduces neuronal death, astrocyte activation, and neurological deficits following ischemia or trauma by preventing aberrant hemichannel opening.

• Demonstrated reduction of infarct size and improved recovery in stroke models.

2. Cardiac Physiology & Arrhythmia Studies

Cx43 hemichannel opening during ischemia-reperfusion contributes to cardiomyocyte injury. GAP19 blocks this pathological opening without interfering with normal electrical conduction.

• Used in myocardial ischemia and ventricular arrhythmia research.

3. Inflammatory Signaling

Cx43 hemichannels mediate ATP and cytokine release from immune cells. GAP19 is used to:

• Block inflammasome activation

• Reduce IL-1β release

• Suppress excessive purinergic signaling

4. Pain & Nociception Research

GAP19 reduces Cx43-dependent neuron–glia signaling implicated in chronic pain models.

5. Vascular Studies

Used in endothelial and smooth muscle models to investigate hemichannel roles in:

• Barrier integrity

• Hypoxia responses

• Atherosclerosis

6. Cell Death, Apoptosis & Oxidative Stress Models

GAP19 inhibits Cx43-mediated membrane permeability changes associated with necrosis and apoptosis.

Peer-Reviewed Literature Summary

GAP19 is one of the most extensively characterized connexin-modulating peptides. Key findings include:

1. Foundational Characterization of GAP19

Wang et al., Molecular Biology of the Cell (2013), and later studies, demonstrated:

• GAP19 selectively inhibits Cx43 hemichannels

• No interference with gap-junction communication

• Mechanism: disruption of CT–CL interaction

  (PubMed ID: 23589491)

2. Neuroprotection & Stroke Models

Freitas-Andrade et al., Neuropharmacology (2019):

• GAP19 reduces brain injury after stroke

• Decreases hemichannel-mediated ATP release

  (PubMed ID: 30753887)

3. Cardiac Ischemia-Reperfusion Protection

Małyszko et al., Cardiovascular Research (ScienceDirect):

• GAP19 prevents Cx43 hemichannel opening in cardiomyocytes

• Improves post-ischemia recovery

4. Inflammation & Cytokine Modulation

Orellana et al., Glia (PubMed):

• GAP19 blocks inflammatory ATP release from astrocytes

• Reduces IL-1β activation

5. Pain, Glial Signaling

Studies in dorsal root ganglia and spinal cord models show GAP19 blocks glial Cx43 hemichannels involved in chronic pain pathways.

Why Choose GAP19 (KQIEIKKFK)

• Highly selective inhibitor of Cx43 hemichannels

• No effect on gap junction coupling (unlike other connexin mimetics)

• Supported by extensive PubMed-indexed literature

• Valuable in cardiac, neural, immune, vascular, metabolic, and cell death research

• Compatible with peptide modifications (FITC, biotin, D-amino acids, PEGylation, cell-penetrating tags) for functional studies