Manganese fluxes and manganese‐dependent neurotransmitter release in presynaptic nerve endings isolated from rat brain.

Abstract

SUMMARY1. The uptake and efflux of 54Mn and 45Ca, and the release of dopamine (DA) were measured in pinched-off presynaptic nerve endings (synaptosomes) isolated from rat brain.2. The uptake of Mn and Ca was increased when forebrain or striatal synaptosomes were incubated in a depolarizing, K-rich solution. The time courses of K-stimulated Mn and Ca entry were similar: there was initially a high rate of ion accumulation, lasting 1-3 s, that gradually levelled off. The initial uptake of Mn, like that of Ca, was greatly diminished by a 10 s pre-incubation in K-rich solution prior to the addition of radiotracer.3. Several Ca channel blockers, including Ni (0 03 mM), Sr (2'0 mM), Co (0 04 mM), Ba (1-5 mM) and La (0-2 mM), suppressed the K-stimulated uptake of Mn and of Ca to a similar extent. The K-stimulated uptake of Mn increased as a function of the external Mn concentration, and saturated at high external concentrations of Mn. These high concentrations of Mn also blocked the K-stimulated uptake of Ca.4. There was a decreased efflux of Ca, but not of Mn, from the synaptosomes when the external Na concentration was reduced. The Na-dependent efflux of Ca was diminished by external Mn, but was unaffected when the synaptosomes were loaded with Mn.5. The rate of [3H]DA release from striatal synaptosomes was less than 0-001 sin non-depolarizing, low-K solutions, in the absence or presence of Mn and Ca (1 mM). The rate ofrelease was also unchanged in depolarizing, K-rich solutions in the absence of these divalent cations. The addition of 1 mM-Mn to a K-rich solution increased the rate of DA release by about 40 %, and the time course of release was linear for at least 30 s. The addition of t mM-Ca increased the rate of release nearly 100-fold during the first second, and thereafter the rate of release rapidly declined.6. Ni (1 mM) and, to a lesser extent, Mg (10 mM) reduced the rate of K-stimulated DA release that is dependent on either Mn or Ca. The pattern of inhibition of DA release resembled the pattern of inhibition of K-stimulated uptake of Mn and Ca.

Behavioral, electrophysiological and histopathological consequences of systemic manganese administration in MEMRI

“…This effect is probably the result of Mn 2+ competition for voltage-gated Ca 2+ channels at the presynaptic terminal [2,3]. This effect on hippocampal neural transmission did not affect, however, neuronal excitability and did not preclude the expression of long-lasting synaptic plasticity.…”

“…is taken up through voltage-gated Ca 2+ channels [2,3]. Although it cannot be applied to humans due to the potential toxicity of the ion (see below), MEMRI has significant advantages, being independent of cerebral blood flow and the nonlinearities of the neurovascular coupling that affect conventional fMRI techniques.…”

Mapping of functional brain activity in freely behaving rats during voluntary running using manganese-enhanced MRI: Implication for longitudinal studies

“…The ability of manganese to cross the BBB following systemic administration (Murphy et al, 1991;Rabin et al, 1993), enter excitable cells via voltage-gated Ca 2+ channels (Drapeau and Nachshen, 1984;Lin and Koretsky, 1997;Narita et al, 1990;Silva et al, 2004) and accumulate in the activated brain regions gives the unique opportunity to use MEMRI for the whole-brain functional mapping. Exposure to subtoxic levels of manganese extends the application of this method to behaving animals.…”

Cocaine-induced brain activation detected by dynamic manganese-enhanced magnetic resonance imaging (MEMRI)

“…In vitro studies in isolated cells (12,13) and in vivo mouse heart (14) demonstrate that Mn 2ϩ enters cells through ligand-or voltagegated Ca 2ϩ channels, an effect blocked by Ca 2ϩ channel antagonists. Once translocated, Mn 2ϩ remains intracellular for a prolonged period (15).…”