Publications by authors named "Kathleen M Giangiacomo"

The alpha-KTx peptide toxins inhibit different types of potassium channels by occluding the outer channel pore composed of four identical alpha subunits. The large-conductance, calcium-activated (BK or Slo1) and voltage-dependent (KV) potassium channels differ in their specificity for the different alpha-KTx subfamilies. While many different alpha-KTx subfamilies of different sizes inhibit KV1 channels with high affinity, only one subfamily, alpha-KTx 1.

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Potassium channel dysfunction underlies diseases such as epilepsy, hypertension, cardiac arrhythmias, and multiple sclerosis. Neurotoxins that selectively inhibit potassium channels, alpha-KTx, have provided invaluable information for dissecting the contribution of different potassium channels to neurotransmission, vasoconstriction, and lymphocyte proliferation. Thus, alpha-KTx specificity comprises an important first step in potassium channel-directed drug discovery for these diseases.

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Potassium channel inhibitor peptides from scorpion venom, alpha-KTx, have greatly advanced our understanding of potassium channel structure and function, Because of their high affinity interaction with the outer pore, alpha-KTx's have aided, in identification of amino acids lining the pore and of proteins constituting functional channels. The alpha-KTx's display a large range of affinities for different potassium channels with differences in binding free energy exceeding approximately 8 kcal/mol. These differences in affinities are the foundation of alpha-KTx specificity and have aided in revealing the physiological and patho-physiological roles of potassium channels.

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Iberiotoxin (IbTX) is a remarkably selective alpha-K toxin peptide (alpha-KTx) inhibitor of the maxi-K channel. In contrast, the highly homologous charybdotoxin inhibits both the maxi-K and K(V)1.3 channels with similar high affinity.

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