PT  - JOURNAL ARTICLE
AU  - T M Norris
AU  - E Moya
AU  - I S Blagbrough
AU  - M E Adams
TI  - Block of high-threshold calcium channels by the synthetic polyamines sFTX-3.3 and FTX-3.3.
DP  - 1996 Oct 01
TA  - Molecular Pharmacology
PG  - 939--946
VI  - 50
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/50/4/939.short
4100  - http://molpharm.aspetjournals.org/content/50/4/939.full
SO  - Mol Pharmacol1996 Oct 01; 50
AB  - A polyamine component of Agelenopsis aperta spider venom designated FTX is reported to be a selective antagonist of P-type calcium channels in the mammalian brain. Consequently, this component has frequently been used as a pharmacological tool to determine the presence, distribution, and function of P-type channels in physiological systems. We describe antagonism of calcium channels by the synthesized polyamine FTX-3.3, which has the proposed structure of natural FTX. We also examined a corresponding polyamine amide, sFTX-3.3. These polyamines are critically evaluated for antagonism of three high-threshold calcium channel subtypes in rat neurons through the use of the whole-cell patch-clamp technique. FTX-3.3 (IC50 = approximately 0.13 mM) is approximately twice as potent as sFTX-3.3 (IC50 = approximately 0.24 mM) against P-type channels and approximately 3-fold more potent against N-type channels (FTX-3.3, IC50 = approximately 0.24 mM; sFTX-3.3, IC50 = approximately 0.70 mM). Both polyamines also block L-type calcium channels with similar potencies. sFTX-3.3 (1 mM) and FTX-3.3 (0.5 mM) typically block 50% and 65% of Bay K8644-enhanced L-type current, respectively. Antagonism of each calcium channel subtype is voltage dependent, with less inhibition of Ba2+ currents at more-positive potentials. These data show that both sFTX-3.3 and FTX-3.3 antagonize P-, N-, and L-type calcium channels in mammalian Purkinje and superior cervical ganglia neurons with similar IC50 values.