How activation of nNAChRs modulates the L-type
(Cav1) channel functioning
nNAChRs have a high Ca2+ permeability (Gotti &
Clementi, 2004), which does not have direct effect on the calcium
transient amplitude. However, the calcium entry through these receptors
can lead to two potential outcomes and one can observe an increase in
the amplitude of the calcium transient as a result of two mechanisms: i)
the CDF process (calcium dependent facilitation) of the
Cav1 type channel is triggered (Kim et al., 2008)
(Figure 8a) ; ii) the CDI (calcium dependent inactivation)
process of Cav1 type calcium channels, mediated by the
interaction between CaM and Ca2+ channel, is disrupted
by increasing CaMKII activity (Abiria & Colbran, 2010) (Figure
8b) . However, according to (Prior & Singh, 2000), decrease in
ACh release caused by activation of nNAChRs is not associated with CaM.
The existence of a functional interaction between nNAChRs and the
channels of the Cav1 type was established in primary
culture of neurons in the mouse cerebral cortex (Katsura et al., 2002).
It should be noted that this work revealed the interaction of calcium
channels with α4β2 nNAChRs (Potentially, a similar interaction takes
place in the muscle-nerve junction). The authors believe that activation
of presynaptic receptors leads to depolarization sufficient for opening
of Cav1 calcium channels and entry of calcium into the
neuron (Katsura et al., 2002) (Figure 8c) .
The results obtained on the neuromuscular preparation suggest that the
Cav1 type of calcium channels is located far from the
active zone (Polo-Parada et al., 2001), therefore,
Ca2+ entering through them cannot directly interact
with the exocytosis machine. It has been shown that there is a
functional interaction between the Cav1 type and
Ca2+-activated K+(KCa) channels (Flink et al., 2003).
We hypothesize that nNAChRs, Cav1 type calcium channels,
and KCa channels can form a cluster on the presynaptic
membrane. Activation of ones starts the process of autoinhibition of ACh
release. In this case, entering Ca2+ through
Cav1 type channels can activate KCachannels, which leads to membrane hyperpolarization and, as a
consequence, a decrease in the amount of released neurotransmitter
quanta. However, this hypothesis will need to be proven in further
research.