Dominant Role of N-Type Ca ²⁺ Channels in Evoked Release of Norepinephrine from Sympathetic Neurons

TLDR

Neurons possess multiple calcium channel types, yet it is unclear which mediate stimulus‑secretion coupling. The study aimed to determine the relative contribution of N‑type and L‑type calcium channels to norepinephrine release in rat sympathetic neurons. N‑type and L‑type channels were compared for voltage dependence, unitary barium conductance, and pharmacology. Nitrendipine blocked L‑type but not N‑type channels, and potassium‑evoked norepinephrine release was largely suppressed by cadmium and ω‑Conus toxin while remaining resistant to nitrendipine, demonstrating that N‑type channels dominate depolarization‑evoked release.

Abstract

Multiple types of calcium channels have been found in neurons, but uncertainty remains about which ones are involved in stimulus-secretion coupling. Two types of calcium channels in rat sympathetic neurons were described, and their relative importance in controlling norepinephrine release was analyzed. N-type and L-type calcium channels differed in voltage dependence, unitary barium conductance, and pharmacology. Nitrendipine inhibited activity of L-type channels but not N-type channels. Potassium-evoked norepinephrine release was markedly reduced by cadmium and the conesnail peptide toxin omega-Conus geographus toxin VIA, agents that block both N- and L-type channels, but was little affected by nitrendipine at concentrations that strongly reduce calcium influx, as measured by fura-2. Thus N-type calcium channels play a dominant role in the depolarization-evoked release of norepinephrine.