DEVELOPMENTAL H³-NITRENDIPINE BINDING IN IMMATURE SPINAL CORD NEURONS WITH INCIDENTAL TTX DISPLACEMENT

Abstract

Ca⁺⁺ may play a role in neurodevelopment through involvement in neurite extension, voltage-sensitive release of neurotransmitters and the expression of genes for enzymes involved in transmitter synthesis. Nitrendipine(NTP), a dihydropyridine, is believed to bind with the voltage-sensitive Ca⁺⁺ channels. The development of voltage-sensitive Ca⁺⁺ channels was studied using H³-NTP.

The developmental curve of H³-NTP in fetal mouse spinal cord cultures shows a multiphasic increase in binding as cultures matured. Day 19 was the point of maximal binding with a plateau phase on days 3-5. The amount of binding was greater (>5 fold) than that for Na⁺ channel ligands at similar developmental periods. Scatchard analysis showed a non-linear relationship of H³-NTP binding(.3-20nM). The two receptor sites showed increasing Kd's and Bmax's throughout development.

Tetrodotoxin (TTX), a Na⁺ channel blocker, was shown to interfere with H³-Nitrendipine (H³-NTP) binding. TTX displacement was seen at 10⁻⁶M concentration with maximal displacement at 10⁻⁶M. The TTX effect was a developmental phenomenon. H³-NTP binding showed 42%, 34% and 21% displacement on days 5, 8 and 23 respectively with 1 μM TTX. Mature cultures (Day 27) showed no significant displacement of H³-NTP with 1 μM TTX. Both receptor sites were sensitive to TTX during early neuro-development. It is concluded that TTX and H³-NTP have binding site similarity in early fetal mouse spinal cord cultures.

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