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Research Service | Cell and Tissue Patch-Clamp Recording and Analysis Services

Time:2025-10-17 15:08:00

Technical Overview

The patch-clamp technique represents a revolutionary breakthrough in modern electrophysiology. With its exceptional precision in capturing electrical signals across cell membranes, it has become a core tool for elucidating cellular physiological functions.

The principle involves using a micropipette puller to draw the tip of a glass microelectrode into a fine opening of approximately 1.5–3.0 μm in diameter. Through gentle negative pressure, the pipette tip forms a gigaohm seal with the cell membrane, electrically isolating the patch of membrane within the tip from its surroundings. By clamping the membrane potential of this isolated region, researchers can precisely monitor and record ion channel currents on the membrane patch.
 
Figure 1. Principle of the patch-clamp technique
 

Core Recording Modes

The patch-clamp technique includes four classical recording modes:
cell-attached mode, inside-out mode, outside-out mode, and conventional whole-cell mode.

Each mode can be flexibly selected according to specific research objectives:

Cell-attached mode is noninvasive and preserves the cell’s native microenvironment, allowing the recording of spontaneous activity from single ion channels.
Inside-out mode exposes the cytoplasmic side of the membrane, enabling the manipulation of intracellular factors and the investigation of channel mechanisms dependent on intracellular signaling.
Outside-out mode exposes the extracellular side of the membrane to the perfusion environment, allowing simulation of extracellular stimuli and assessment of ligand-gated channel drug sensitivity.
Whole-cell mode ruptures the membrane patch to record integrated neuronal electrical activity, suitable for studying action potentials, postsynaptic currents, and neuronal excitability.

Figure 2. Four basic recording modes of the patch-clamp technique

Service Scope

1. Cell Patch-Clamp Recording

This service covers a wide range of cell types, including neuronal cells, cardiomyocytes, muscle cells, stem cells, and immune cells. It enables precise recording of single-cell membrane currents, action potentials, and receptor–channel kinetics, providing insights into the key roles of ion channels in cellular excitability, signal transduction, and drug actions.

2. Brain Slice Patch-Clamp Recording

This service focuses on acute brain slices from various brain regions. It allows analysis of synaptic transmission at the single-cell level while preserving local microcircuits. Supporting studies on LTP/LTD, network oscillations, and neuropharmacology, it provides high-fidelity data for exploring brain function and disease mechanisms.
  
Detection Object Recording Target Indicator Significance
Brain Slice
Patch-Clamp
Action potential (AP) Firing frequency, resting membrane potential (RMP), membrane resistance (Rm), threshold (AP threshold) Reflects the pattern of neuronal electrical activity
Miniature excitatory/inhibitory postsynaptic currents (mEPSC/mIPSC), spontaneous excitatory/inhibitory postsynaptic currents (sEPSC/sIPSC) Frequency, amplitude Reflects pre- and postsynaptic transmission functions
Long-term potentiation/depression (LTP/LTD) Slope of field excitatory postsynaptic potential (fEPSC) Reflects synaptic plasticity related to learning and memory
Cell Patch-Clamp Ion currents through potassium, sodium, calcium, and other channels Current density (pA/pF) Reflects ion channel functions and drug mechanisms of action



Service Workflow

01. Requirement Communication:
Define research objectives, cell types, tissue sample types, and measurement parameters.

02. Customized Experimental Design:
Develop a tailored experimental plan based on research needs, including selection of recording mode, optimization of stimulation paradigms, and determination of sample size.

03. Cell Culture / Tissue Preparation:
Perform cell line culturing and mouse brain slice preparation and pretreatment to ensure samples meet experimental requirements.

04. Signal Recording:
Use high-precision patch-clamp systems to capture electrical signals, with real-time monitoring of data quality.

05. Data Analysis:
Conduct statistical analysis using professional software such as pClamp to ensure accuracy and reliability.

06. Result Delivery:
Provide raw data, analyzed results, and a comprehensive experimental report.

The experimental cycle typically takes about one month, with the exact duration depending on the complexity of the experimental design.

Deliverables

Raw Data: Original signal recording files in pClamp format.
Analysis Results: Statistical summaries of valid data and intergroup comparison tables.
Project Report: Includes experimental methods, analytical figures, and conclusions—providing a complete presentation of the experimental process and results.

 

Service Case Studies

Case 1:

To investigate the mechanisms by which chronic restraint stress affects cost–benefit decision-making, adult male C57BL/6J mice were randomly divided into a control group (Control) and an experimental group (Exp, chronic restraint stress group). Mice in the experimental group were restrained for 6 hours per day for 14 consecutive days to simulate chronic stress in humans, while the control group was not restrained. Coronal brain slices (300 μm thick) containing the prelimbic cortex (PL) were then prepared and incubated in continuously oxygenated artificial cerebrospinal fluid (aCSF) at 32°C.

APs were recorded from layer V pyramidal neurons in the PL region using whole-cell current-clamp mode. The initial resting membrane potential was set at -70 mV, and depolarizing current steps of 0–140 pA (increments of 20 pA, duration 600 ms) were applied. Results showed that at stimulation intensities of 100, 120, and 140 pA, the number of APs in the experimental group was significantly higher than in the control group (P < 0.01), while resting membrane potential (RMP) and membrane resistance (Rm) showed no significant differences between groups. This suggests that chronic restraint stress increases the gain of PL pyramidal neurons, causing decision-related microcircuits to exhibit hyperactivity in response to the same input, thereby disrupting value encoding and inducing short-sighted decision bias.

Figure 3: AP recording results—representative traces at different stimulation intensities and statistical comparisons of AP number, RMP, and Rm between groups.


Case 2:

To explore the synaptic mechanisms by which high-fat diet (HFD)-induced obesity affects memory flexibility, 8-week-old male C57BL/6J mice were randomly assigned to a control group (Control) and an experimental group (Exp). The control group was fed standard chow, while the experimental group was fed a high-fat diet for 12 weeks to establish a diet-induced obesity model.

Horizontal brain slices (300 μm thick) containing the dorsal hippocampal CA1 region were prepared and maintained in aCSF at 32°C. Using whole-cell voltage-clamp mode, spontaneous excitatory postsynaptic currents (sEPSCs) and spontaneous inhibitory postsynaptic currents (sIPSCs) were recorded at holding potentials of -70 mV and 0 mV, respectively. Ten valid neurons were recorded per group, and each neuron was continuously recorded for 5 minutes.

Compared to the control group, the experimental group showed significantly increased frequency and amplitude of sEPSCs (P < 0.001) and sIPSCs (P < 0.01), suggesting that long-term high-fat intake synergistically enhances excitatory–inhibitory synaptic strength in CA1 pyramidal neurons, thereby affecting hippocampal circuits related to memory.

Figure 4: sEPSC and sIPSC recording results—representative traces and statistical comparisons of frequency and amplitude between groups.
 


Case 3:

To investigate the mechanism by which early social isolation (ISO) increases adult aggression through excitatory–inhibitory imbalance in the prefrontal cortex, male C57BL/6J mice were randomly assigned to a group-housed control group (Control, 5 mice per cage) or a social isolation group (ISO, single-housed from P21 to P63). At P63, medial prefrontal cortex (mPFC) pyramidal neurons were acutely isolated, and recordings were completed within 4 hours after neuron isolation.

Whole-cell voltage-clamp recordings were performed with a voltage protocol holding at -100 mV and stepping from -60 to +60 mV (20 mV increments, 50 ms duration, 5 s interval). P/4 online leak subtraction was applied to correct leak currents, allowing specific recording of voltage-gated sodium currents (Nav currents).


Results showed that at holding potentials of -40 mV and -20 mV, peak Nav current density in the experimental group was significantly higher than in controls (P < 0.05), indicating that early social isolation upregulates Nav current density in mPFC pyramidal neurons. This enhances neuronal excitability, disrupts excitatory–inhibitory balance, and ultimately leads to increased aggression in adulthood.

Figure 5: Sodium channel recording results—representative traces of Nav currents at different holding potentials and statistical comparisons of current density between groups.

 

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