TRPC4 and GIRK channels underlie neuronal coding of firing patterns that reflect G q/11 –G i/o coincidence signals of variable strengths

Author:

Tian Jin-bin1ORCID,Yang Jane23ORCID,Joslin William C.1ORCID,Flockerzi Veit4ORCID,Prescott Steven A.235ORCID,Birnbaumer Lutz67ORCID,Zhu Michael X.1ORCID

Affiliation:

1. Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030

2. Neurosciences & Mental Health, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada

3. Institute of Biomedical Engineering, University of Toronto, Toronto, ON M5S 3G9, Canada

4. Experimental and Clinical Pharmacology and Toxicology, Saarland University, Homburg, 66421, Germany

5. Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada

6. Institute for Biomedical Research (BIOMED UCA-CONICET), School of Medical Sciences, Catholic University of Argentina (UCA), Buenos Aires, C1107AFF, Argentina

7. Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709

Abstract

Significance Neurons communicate by releasing neurotransmitters, many of which act at G protein–coupled receptors. Although it is well known that G q/11 accelerates action potential firing while G i/o inhibits firing, how firing patterns change in response to simultaneous activation of G q/11 and G i/o remains elusive, especially because the relative strength of G q/11 versus G i/o activation varies greatly from event to event. This study reveals that neurons encode distinct messages that reflect coincident G q/11 and G i/o stimulation by activating two ion channels, TRPC4 and GIRK. The resulting firing patterns, composed of burst, pause, and firing recovery phases, reflect both the occurrence of coincident G q/11 and G i/o activation and their relative strengths. With these, we may begin to interpret the language of neurons.

Funder

HHS | NIH | National Institute of Neurological Disorders and Stroke

HHS | NIH | National Institute of Environmental Health Sciences

Deutsche Forschungsgemeinschaft

Canadian HIV Trials Network, Canadian Institutes of Health Research

Hospital for Sick Children

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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