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L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons

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Abstract

As a noninvasive technique, ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo. The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons. However, the underlying mechanism of low-intensity pulsed ultrasound (LIPUS)-induced neuro-modulation effects is still unclear. Here, we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca2+ homeostasis in cultured hippocampal neurons. By whole-cell patch clamp recording, we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents (sEPSCs) and also increases the amplitude of sEPSCs in hippocampal neurons. This phenomenon lasts for > 10 min after LIPUS exposure. Together with Ca2+ imaging, we clarified that LIPUS increases the [Ca2+]cyto level by facilitating L-type Ca2+ channels (LTCCs). In addition, due to the [Ca2+]cyto elevation by LIPUS exposure, the Ca2+-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression. Our work suggests that LIPUS regulates neuronal activity in a Ca2+-dependent manner via LTCCs. This may also explain the multi-activation effects of LIPUS beyond neurons. LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca2+ influx.

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Acknowledgements

This work was supported by the National Key Research & Development Program of China (2022YFC3602700 and 2022YFC3602702), the Science and Technology Innovation 2030—Brain Science and Brain-Inspired Intelligence Project (2021ZD0201301), the National Natural Science Foundation of China (32170688, 31971159, and 12034015), the Innovation Program of Shanghai Municipal Education Commission (2019-01-07-00-07-E00041), the Shanghai Municipal Science and Technology Major Project (2018SHZDZX01), the ZJ Lab, the Shanghai Center for Brain Science and Brain-Inspired Technology, the Program of Shanghai Academic Research Leaders (21XD1403600), and the Fundamental Research Funds for the Central Universities (22120230562).

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Authors and Affiliations

  1. State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, 200433, China

    Wen-Yong Fan, Yu-Qi Wang, Jia-Qi Hu, Wen-Xu Tang & Lei Xue

  2. Department of Physiology and Neurobiology, School of Life Sciences, Fudan University, Shanghai, 200438, China

    Wen-Yong Fan, Yu-Qi Wang, Jia-Qi Hu, Wen-Xu Tang & Lei Xue

  3. Institute of Acoustics, School of Physics Science and Engineering, Tongji University, Shanghai, 200092, China

    Yi-Ming Chen, Yi-Fan Wang & Qian Cheng

  4. Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Tongji University, Shanghai, 200070, China

    Yi-Ming Chen, Yi-Fan Wang & Qian Cheng

  5. Center for Rehabilitation Medicine, Department of Pain Management, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, China

    Jia-Qi Hu

  6. Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China

    Yi Feng

  7. Shanghai Research Institute for Intelligent Autonomous Systems, Tongji University, Shanghai, 201210, China

    Qian Cheng

  8. Research Institute of Intelligent Complex Systems, Fudan University, Shanghai, 200433, China

    Lei Xue

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  1. Wen-Yong Fan
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Fan, WY., Chen, YM., Wang, YF. et al. L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons. Neurosci. Bull. (2024). https://doi.org/10.1007/s12264-024-01186-2

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