biostudies-literatureXiong AHHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)NIAAA NIH HHSNINDS NIH HHSHHS | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)NIH HHSe2404969121https://www.ebi.ac.uk/biostudies/studies/S-EPMC11363341biostudies-literatureUnknown121(35)The abundance of CaV2 voltage-gated calcium channels is linked to presynaptic homeostatic plasticity (PHP), a process that recalibrates synaptic strength to maintain the stability of neural circuits. However, the molecular and cellular mechanisms governing PHP and CaV2 channels are not completely understood. Here, we uncover a previously not described form of PHP in <i>Caenorhabditis elegans</i>, revealing an inverse regulatory relationship between the efficiency of neurotransmitter release and the abundance of UNC-2/CaV2 channels. Gain-of-function <i>unc-2SL(S240L)</i> mutants, which carry a mutation analogous to the one causing familial hemiplegic migraine type 1 in humans, showed markedly reduced channel abundance despite increased channel functionality. Reducing synaptic release in theProceedings of the National Academy of Sciences of the United States of AmericaPresynaptic neurons self-tune by inversely coupling neurotransmitter release with the abundance of CaV2 voltage-gated Ca&lt;sup&gt;2+&lt;/sup&gt; channels.PMC11363341R21 AA029811R21AA029811R21 NS139113R21NS139113P40 OD010440Kim HXiong ARichmond JEfalsePresynaptic neurons self-tune by inversely coupling neurotransmitter release with the abundance of CaV2 voltage-gated Ca&lt;sup&gt;2+&lt;/sup&gt; channels.The abundance of CaV2 voltage-gated calcium channels is linked to presynaptic homeostatic plasticity (PHP), a process that recalibrates synaptic strength to maintain the stability of neural circuits. However, the molecular and cellular mechanisms governing PHP and CaV2 channels are not completely understood. Here, we uncover a previously not described form of PHP in <i>Caenorhabditis elegans</i>, revealing an inverse regulatory relationship between the efficiency of neurotransmitter release and the abundance of UNC-2/CaV2 channels. Gain-of-function <i>unc-2SL(S240L)</i> mutants, which carry a mutation analogous to the one causing familial hemiplegic migraine type 1 in humans, showed markedly reduced channel abundance despite increased channel functionality. Reducing synaptic release in the2024-01-01T00:00:00Z2024 Aug2025-04-03T23:17:00.539Z2025-04-03T23:17:00.539ZS-EPMC113633413917278310.1073/pnas.2404969121