biostudies-literatureWeir KChicago Community TrustNew York Stem Cell FoundationSwiss National Science FoundationNIDDK NIH HHSAlfred P. Sloan FoundationNINDS NIH HHSNational Institutes of HealthNIH HHSNIGMS NIH HHSEsther A. and Joseph Klingenstein Funde57578https://www.ebi.ac.uk/biostudies/studies/S-EPMC7250568biostudies-literatureUnknown9All animals detect and integrate diverse environmental signals to mediate behavior. Cnidarians, including jellyfish and sea anemones, both detect and capture prey using stinging cells called nematocytes which fire a venom-covered barb via an unknown triggering mechanism. Here, we show that nematocytes from <i>Nematostella vectensis</i> use a specialized voltage-gated calcium channel (nCa_V) to distinguish salient sensory cues and control the explosive discharge response. Adaptations in nCa_V confer unusually sensitive, voltage-dependent inactivation to inhibit responses to non-prey signals, such as mechanical water turbulence. Prey-derived chemosensory signals are synaptically transmitted to acutely relieve nCa_V inactivation, enabling mechanosensitive-triggereLifeA molecular filter for the cnidarian stinging response.PMC7250568P400PB-180894180894P2SKP3-187684Searle Scholars ProgramR35 GM142697P2SKP3_187684187684Robertson Neuroscience InvestigatorKlingenstein-Simons FellowshipF31 NS117055R00DK115879U24 NS109102R00 DK1158791F31NS117055Weir KBellono NWvan Giesen LDupre CLee ASfalseA molecular filter for the cnidarian stinging response.All animals detect and integrate diverse environmental signals to mediate behavior. Cnidarians, including jellyfish and sea anemones, both detect and capture prey using stinging cells called nematocytes which fire a venom-covered barb via an unknown triggering mechanism. Here, we show that nematocytes from <i>Nematostella vectensis</i> use a specialized voltage-gated calcium channel (nCa_V) to distinguish salient sensory cues and control the explosive discharge response. Adaptations in nCa_V confer unusually sensitive, voltage-dependent inactivation to inhibit responses to non-prey signals, such as mechanical water turbulence. Prey-derived chemosensory signals are synaptically transmitted to acutely relieve nCa_V inactivation, enabling mechanosensitive-trigger2020-01-01T00:00:00Z2020 May2026-05-04T02:05:03.917Z2020-06-01T07:06:00ZS-EPMC72505683245238410.7554/eLife.57578