The Ukrainian Scientist Rewiring Our Understanding of the Brain
Author(s): Scott Douglas Jacobsen
Publication (Outlet/Website): International Policy Digest
Publication Date (yyyy/mm/dd): 2025/11/12
Prof. Oleg Krishtal is a Ukrainian neurophysiologist and a pioneer in ion-channel research at the Bogomoletz Institute of Physiology, part of the National Academy of Sciences of Ukraine. Trained in molecular physics, he has led the Department of Cellular Membranology since 1982 and served as the institute’s director from 2011 to 2021.
A foundational figure in modern ion-channel physiology, Krishtal conducted the first intracellular perfusion of a nerve cell (Nature, 1975), first described acid-sensing ion channels (ASICs), and identified ionotropic ATP (P2X) receptors in mammalian sensory neurons. A member of both the National Academy of Sciences of Ukraine and Academia Europaea, his department investigates membrane proteins in neurons, networks, and organs—research that illuminates the biology of pain, synaptic signaling, ischemia, and neurological disease.
In this conversation, Krishtal explores his pioneering work on ASICs and P2X receptors, emphasizing their critical roles in brain function, ischemia, epilepsy, and pain. He describes his lab’s advanced electrophysiological methods—from patch-clamp recordings to in vivo EEG and ex vivo preparations that connect cellular mechanisms to behavior. Krishtal also discusses collaborations with Ukrainian chemists and plans for international partnerships to develop ASIC-targeting therapeutics.
Finally, he reflects on the challenges of conducting neuroscience in wartime—repairing equipment, preserving samples, and adapting under constant disruption—illustrating how persistence and ingenuity keep scientific progress alive amid extraordinary adversity.
The following interview was edited for clarity and length.
Scott Douglas Jacobsen: Let’s start with your research program before turning to the challenges of working through a war. What are your lab’s main scientific goals for ASIC and P2X receptor studies looking ahead to 2030?
Oleg Krishtal: We will focus on the study of ASICs—their pharmacology and physiological roles. Interest in ASICs has grown steadily. Forty-five years after their discovery, it is now clear that members of the ASIC family are expressed in nearly every mammalian neuron, both in the brain and the periphery. They participate in numerous functions, though the list is far from complete. The few pharmacological tools currently available suggest that targeting ASICs may aid in conditions such as brain ischemia, epilepsy, pain, and multiple sclerosis. More recently, inhibition of ASICs has also shown promise against jaundice.
Despite their involvement in many physiological processes, ASIC knockout (ASIC⁻/⁻) animals remain viable, making these channels appealing targets for the development of effective yet safe pharmacological agents. We collaborate closely with Ukrainian chemists—world-class experts in chemical synthesis, computational chemistry, molecular dynamics, and rational drug design. Our current work is supported by the National Research Foundation of Ukraine, but we aim to establish large international consortia with colleagues across the EU, UK, and the United States.
Several small-molecule ASIC inhibitors have previously advanced to the point of clinical application, yet all ultimately failed in trials. We believe that a multidisciplinary approach and new molecular strategies can change this outcome.
Jacobsen: How do ion channels on the cell membrane and those at the nuclear envelope together form a unified model of how neurons function?
Krishtal: Channels located on the cell membrane are responsible for information processing—electric excitation and synaptic transmission. Some also serve “housekeeping” functions. Because acid–base balance is a key aspect of homeostasis, it is plausible that ASICs play an important role here as well, though this remains to be investigated.
Channels at the nuclear envelope primarily regulate the transport of molecules, including genetic material. Together, both channel systems act in concert to ensure proper neuronal function.
Jacobsen: Which disease areas do you see as the top priorities for ASIC and P2X receptor research?
Krishtal: At the moment, ischemic damage—not only stroke but also jaundice, which can irreversibly harm the brains of newborns—is our main target for developing ASIC pharmacology. Our preliminary findings also place epilepsy high on the list. Data on the pathological role of ASICs in multiple sclerosis are still limited, but existing evidence is highly significant and may guide new approaches to this devastating disease.
Moreover, many studies suggest that local acidosis resulting from inflammation accompanies a broad range of brain disorders—not only neurological but psychiatric as well. The role of ASICs across such pathologies warrants intensive investigation.
Jacobsen: What are the core methodologies driving your lab’s work today—patch-clamp recording, fast pH imaging, genetic reporters, or others?
Krishtal: Our laboratory is primarily focused on electrophysiological research. We are among the leading manual electrophysiology labs in the world. Using various patch-clamp configurations, we study ion-channel activity in cell nuclei, a wide range of acutely isolated mammalian cell types, and established cell lines.
We have developed automated systems for pharmacological studies of ion channels, allowing experiments with extremely small quantities of test substances—as little as 200 µL per concentration point—making it possible to study peptides isolated from diverse venoms. We also conduct ex vivo experiments on acute brain slices and isolated nerve fibers using the skin–nerve preparation model.
Recently, we incorporated in vivo recordings of nerve-fiber activity and intracranial electroencephalography (iEEG) in freely moving animals. These techniques require advanced surgical and anesthetic skills, and we are proud that roughly 95 percent of animals survive the implantation of brain electrodes.
Unfortunately, financial constraints—exacerbated by the war—have limited our ability to expand into molecular biology, optogenetics, and advanced imaging.
Jacobsen: How do you connect single-cell findings to behavioral outcomes in your animal models?
Krishtal: We build this link through a multi-level experimental strategy combining electrophysiological, pharmacological, and behavioral approaches. At the single-cell level, we use patch-clamp recordings to identify specific ionic mechanisms and drug responses in neurons expressing ASICs or other ion channels of interest. These data allow us to characterize how pathological or pharmacological interventions alter cellular excitability.
To connect these findings to system-level and behavioral outcomes, we extend our studies to ex vivo and in vivo models. Ex vivo brain-slice preparations bridge isolated cell responses and network activity. In vivo, we perform extracellular recordings of central neural activity and intracranial EEG monitoring in freely moving animals to assess how modulation of ASICs and related targets affects seizure susceptibility, sleep, and other functions. Ex vivo skin–nerve preparations enable us to measure primary nociceptor signals, providing a physiological readout of pain stimuli.
By integrating cellular and tissue electrophysiology with behavioral measures—nociceptive thresholds, locomotion, cognitive performance—we can directly correlate cellular biophysics with observable behavior. This integrative design helps identify causal relationships between molecular mechanisms and functional outcomes, strengthening the translational potential of single-cell data.
Jacobsen: What day-to-day adjustments have allowed your lab to keep working during the war? And how have power outages, Internet loss, and supply disruptions affected your experimental timelines?
Krishtal: Our team must be brave, cautious, and inventive. Scientists often take on tasks beyond their expertise—repairing equipment, caring for experimental animals, safeguarding vital samples and data representing years of work, and more. The winter is only beginning, but the lessons from last year—a very difficult one—taught us a great deal.
Jacobsen: Which practices developed during the war do you expect will continue once it’s over?
Krishtal: These are less “practices” than adaptive capacities that have developed rapidly. We believe in the resolve and strength of our people and remain deeply grateful for international support.
Jacobsen: Thank you for your time, Oleg.
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