Nifedipine-Mediated Mobilization of Intracellular Calcium Stores Increases Spontaneous Neurotransmitter Release at Neonatal Rat Motor Nerve Terminals

Abstract

The modulation of spontaneous release of acetylcholine by specific Ca 2ϩ channel blockers was studied at neonatal rat neuromuscular junction. During early postnatal periods (0 -4 days), blockers of N-and P/Q-type Ca 2ϩ channels did not affect miniature endplate potential (MEPP) frequency. Unexpectedly, treatment with the L-type Ca 2ϩ channel antagonist nifedipine, although not when treated with isradipine, nitrendipine, or calciseptine, resulted in strong increase in MEPP frequency. The potentiation effect of nifedipine was dose-dependent with a 56-fold maximum effect with 15 M. The effect decreased during the first two postnatal weeks and disappeared by the third. The effect of nifedipine was not dependent on extracellular Ca 2ϩ and was not altered by the presence of other Ca 2ϩ channel blockers. In contrast, it was abolished by depleting intracellular Ca 2ϩ stores with 2 M thapsigargin and was partially inhibited by 10 M ryanodine. In conclusion, we report a new ryanodine receptor-mediated effect of nifedipine on neonatal neuromuscular junction that may indicate the developmental expression of a specific receptor channel that interacts with intracellular Ca 2ϩ stores. This effect of nifedipine should also be considered when using this drug as either a therapeutic or a research tool.

Anaesthetic Tricaine Acts Preferentially on Neural Voltage-Gated Sodium Channels and Fails to Block Directly Evoked Muscle Contraction

“…2B). When the drugs were washed out with fish water, movement returned to the level elicited by nifedipine alone, consistent with the known irreversible action of nifedipine [46], [47]. Nifedipine did not reduce motility in fixe mutants (data not shown).…”

Ca2+ entry-independent effects of L-type Ca2+ channel modulators on Ca2+ sparks in ventricular myocytes

“…This makes physical interaction a likely candidate for DHPR-RyR2 communication in the heart. Furthermore, DHPR-RyR interactions have also been described in nonmuscle tissues such as neurons (15,37). Therefore, physical DHPR-RyR interactions appear not to be an exclusive characteristic of skeletal muscle.…”

Calcium control of gene regulation in rat hippocampal neuronal cultures

“…3A). Nifedipine increased significantly also the burst frequency from 0.05 AE 0.03 Hz to 0.13 AE 0.05 Hz, probably by interfering with mechanisms controlling synaptic release (Hirasawa and Pittman, 2003;Piriz et al, 2003). Therefore, the effect of two other dihydropyridines-nitrendipine and nimodipineknown to block L-type VGCCs without interfering with the synaptic release, were tested.…”