Inhibitory modulation of action potentials in crayfish motor axons by fluoxetine.

The goal of this report is to explore how K2P channels modulate axonal excitability by using the crayfish ventral superficial flexor preparation. This preparation allows for simultaneous recording of motor nerve extracellular action potentials (eAP) and intracellular excitatory junctional potential (EJP) from a muscle fiber. Previous pharmacological studies have demonstrated the presence of K2P-like channels in crayfish. Fluoxetine (50 µM) was used to block K2P channels in this study. The blocker caused a gradual decline, and eventually complete block, of motor axon action potentials. At an intermediate stage of the block, when the peak-to-peak amplitude of eAP decreased to ∼60%-80% of the control value, the amplitude of the initial positive component of eAP declined at a faster rate than that of the negative peak representing sodium influx. Furthermore, the second positive peak following this sodium influx, which corresponds to the after-hyperpolarizing phase of intracellularly recorded action potentials (iAP), became larger during the intermediate stage of eAP block. Finally, EJP recorded simultaneously with eAP showed no change in amplitude, but did show a significant increase in synaptic delay. These changes in eAP shape and EJP delay are interpreted as the consequence of depolarized resting membrane potential after K2P channel block. In addition to providing insights to possible functions of K2P channels in unmyelinated axons, results presented here also serve as an example of how changes in eAP shape contain information that can be used to infer alterations in intracellular events. This type of eAP-iAP cross-inference is valuable for gaining mechanistic insights here and may also be applicable to other model systems.

Spatial co-occurrence of firearm homicides and opioid overdose deaths in Chicago by level of COVID-19 mortality, 2017-2021.

BACKGROUND: Firearm homicide and opioid overdoses were already leading causes of death in the U.S. before both problems surged during the COVID-19 pandemic. Firearm violence, overdoses, and COVID-19 have all disproportionately harmed communities that are socially and economically marginalized, but the co-occurrence of these problems in the same communities has received little attention. To describe the co-occurrence of firearm homicides and opioid overdose deaths with COVID-19 mortality we used 2017-2021 medical examiner's data from Chicago, IL. Deaths were assigned to zip codes based on decedents' residence. We stratified zip codes into quartiles by COVID-19 mortality rate, then compared firearm homicide and fatal opioid overdose rates by COVID-19 quartile. FINDINGS: Throughout the study period, firearm homicide and opioid overdose rates were highest in the highest COVID-19 mortality quartile and lowest in the lowest COVID-19 mortality quartile. Increases in firearm homicide and opioid overdose were observed across all COVID-19 mortality quartiles. CONCLUSIONS: High co-occurrence of these deaths at the community level call for addressing the systemic forces which made them most vulnerable before the pandemic. Such strategies should consider the environments where people reside, not only where fatal injuries occur.