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

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.

Mechanisms of Exocytosis in Insulin‐Secreting B‐Cells and Glucagon‐Secreting A‐Cells

“…Despite many similarities of the exocytotic machinery in (neuro-) endocrine cells and that in neurotransmitter-releasing fast synapses, there are important differences: 1) synaptic vesicles are small (diameter Ͻ30 nm; von Gersdorff 1996) compared with peptide containing vesicles (hundreds of nm; Plattner et al 1997;Olofsson et al 2002); 2) synaptic exocytosis occurs without delay after the influx of Ca 2π and is at least one order-of magnitude faster than peptide secretion (Ämmälä et al 1993;Mennerick & Matthews 1996); 3) synaptic vesicles may stay largely intact during exocytosis and are refilled with new transmitter molecules immediately after endocytosis, whereas peptide-containing granules are assembled and filled with secretory peptides in the Golgi apparatus (Betz & Bewick 1992;Hutton 1994); 4) synaptic exocytosis generally requires higher concentrations of Ca 2π (Ämmälä et al 1993;Mennerick & Matthews 1996, Chow et al 1996Bollmann et al 2000); and 5) although most secretory cells contain more than one type of voltage-gated Ca 2π -channel, synaptic transmitter exocytosis depends on the faster N-or P-type (Hirning et al 1988;Uchitel et al 1992), whereas endocrine cells preferentially use the L-type (Lopez et al 1994;Barg et al 2001a). Taken together, the findings in neurones suggest that the site of Ca 2π -influx is within minimal distance of the Ca 2π -sensor at the synaptic vesicle and functionally associated within release sites.…”

Presynaptic plasticity: The regulation of Ca2+-dependent transmitter release

“…The most common opinion appears to favour an association between presynaptic secretion and the aga/FTX-and ~o-conotoxin sensitive Ca 2 + channels (Reynolds et al, 1986;Miller, 1986;Hirning et al, 1988;Herdon and Nahorski, 1989;Keith et al, 1989;Maggi et al, 1990;Woodward et al, 1988;Lundy et al, 1992;Pocock and Nicholls, 1992). The ~o-conotoxins inhibit Ca 2 + uptake into, and catecholamine release from, synaptosomes (Reynolds et al, 1986;Woodward, 1988;Rivier, 1987;Pocock and Nieholls, 1992), acetylcholine release (Yeager et al, 1987;Abroad and Miljanich, 1988), serotonin release (Reynolds et al, 1986), vasopressin release (Dayanithi et al, 1988) and dynorphin release (Tertian et al, 1989).…”

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel

“…14,15 Cilnidipine, a new type of CCB that blocks the N-type calcium channel and the L-type calcium channel, is therefore thought to affect bone metabolism, possibly through the inhibition of both the sympathetic nervous system and the voltage-dependent calcium channel. [16][17][18][19] b-blockers are known to affect the relationship between the sympathetic nervous system and bone metabolism, leading to increased BMD. 20,21 Thus, in this study, we investigated the effects of cilnidipine on bone metabolism in comparison with those of amlodipine, an L-type dihydropyridine CCB, and carvedilol, a b-blocker that is known to reduce fracture risk though the inhibition of osteoclast activation via b2-adrenergic receptors, in an ovariectomy-induced rat osteoporosis model.…”