TY - JOUR
T1 - Isoform-specific effects of a novel BmK 11(2) peptide toxin on Na channels
AU - Kondratiev, Andrei
AU - Hahin, Richard
AU - Tomaselli, Gordon F.
N1 - Funding Information:
This work was supported by T32 HL07227-24 training grant to AK and by NIH R01 HL-50411 to GFT.
PY - 2003/3/1
Y1 - 2003/3/1
N2 - BmK 11(2) is a 7216Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch. Nanomolar concentrations of the toxin prolong amphibian nerve action potentials without attenuation of the amplitude. The pharmacological action of the toxin and its sequence similarity to other α-scorpion toxins suggest that BmK 11(2) selectively alters voltage-gated Na channels. In order to test whether BmK 11(2) preferentially modulates the gating or kinetics of certain channel isoforms, we applied BmK 11(2) to muscle, heart and neuronal Na channels. 100nM BmK 11(2) increased the peak current amplitude of skeletal muscle (μ1) and neuronal (N1E-115) Na currents by 40 and 20%, respectively, and reduced the cardiac Na (hH1) current by 15%. The toxin slowed current decay of all isoforms, most prominently in N1E-115 (τBmK/τControl=12), μ1 (11), and less so for hH1 (1.3). BmK 11(2) shifted the voltage dependence of activation of μ1 and N1E-115 currents. BmK 11(2) had no effect on steady-state inactivation, use-dependent availability, and the kinetics of entry into slowly recovering inactivated states.
AB - BmK 11(2) is a 7216Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch. Nanomolar concentrations of the toxin prolong amphibian nerve action potentials without attenuation of the amplitude. The pharmacological action of the toxin and its sequence similarity to other α-scorpion toxins suggest that BmK 11(2) selectively alters voltage-gated Na channels. In order to test whether BmK 11(2) preferentially modulates the gating or kinetics of certain channel isoforms, we applied BmK 11(2) to muscle, heart and neuronal Na channels. 100nM BmK 11(2) increased the peak current amplitude of skeletal muscle (μ1) and neuronal (N1E-115) Na currents by 40 and 20%, respectively, and reduced the cardiac Na (hH1) current by 15%. The toxin slowed current decay of all isoforms, most prominently in N1E-115 (τBmK/τControl=12), μ1 (11), and less so for hH1 (1.3). BmK 11(2) shifted the voltage dependence of activation of μ1 and N1E-115 currents. BmK 11(2) had no effect on steady-state inactivation, use-dependent availability, and the kinetics of entry into slowly recovering inactivated states.
KW - BmK 11(2)
KW - Na channel isoforms
KW - Scorpion Buthus martensii Karsch
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U2 - 10.1016/S0041-0101(02)00286-6
DO - 10.1016/S0041-0101(02)00286-6
M3 - Article
C2 - 12565748
AN - SCOPUS:0037355655
SN - 0041-0101
VL - 41
SP - 269
EP - 276
JO - Toxicon
JF - Toxicon
IS - 3
ER -