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  • Title: Phoneutria nigriventer toxin Tx3-1 blocks A-type K+ currents controlling Ca2+ oscillation frequency in GH3 cells.
    Author: Kushmerick C, Kalapothakis E, Beirão PS, Penaforte CL, Prado VF, Cruz JS, Diniz CR, Cordeiro MN, Gomez MV, Romano-Silva MA, Prado MA.
    Journal: J Neurochem; 1999 Apr; 72(4):1472-81. PubMed ID: 10098851.
    Abstract:
    GH3 cells present spontaneous Ca2+ action potentials and oscillations of intracellular Ca2+, which can be modified by altering the activity of K+ or Ca2+ channels. We took advantage of this spontaneous activity to screen for effects of a purified toxin (Tx3-1) from the venom of Phoneutria nigriventer on ion channels. We report that Tx3-1 increases the frequency of Ca2+ oscillations, as do two blockers of potassium channels, 4-aminopyridine and charybdotoxin. Whole-cell patch clamp experiments show that Tx3-1 reversibly inhibits the A-type K+ current (I(A)) but does not block other K+ currents (delayed-rectifying, inward-rectifying, and large-conductance Ca2+-sensitive) or Ca2+ channels (T and L type) in these cells. In addition, we describe the sequence of a full cDNA clone of Tx3-1, which shows that Tx3-1 has no homology to other known blockers of K+ channels and gives insights into the processing of this neurotoxin. We conclude that Tx3-1 is a selective inhibitor of I(A), which can be used to probe the role of this channel in the control of cellular function. Based on the effect of Tx3-1, we suggest that I(A) is an important determinant of the frequency of Ca2+ oscillations in unstimulated GH3 cells.
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