Cell-attached recording 2026-10-13
In cell-attached recording, the membrane under the patch pipette remains intact and the cytosol is retained. If bath voltage is zero, cell-interior voltage is and pipette voltage is , the patch's inside-minus-outside membrane potential is . Commanding alone does not determine that difference when is unknown or changing. This is especially relevant to single-channel current-voltage relations.
Patch clamp 2026-10-13
Patch clamp connects an electrode to a small area of cell membrane through a solution-filled patch pipette. A gigaohm seal around the rim makes tiny electric currents through ion channels distinguishable from seal leak current. The beautiful change of scale is from a population's average response to individual opening and closing events in single-channel recording.
Separate two questions. The configuration determines which cell membrane is accessible: an intact patch in cell-attached recording, an excised inside-out patch or outside-out patch, or intracellular access in whole-cell recording. The recording mode determines what is commanded and what is observed: voltage clamp commands an electric potential difference and measures electric current; current clamp commands electric current and measures membrane potential. Whole-cell recording supports both modes. A patch can contain several ion channels; a small recording area does not establish that only one is present.
Figure 1.
Patch clamp configurations and synthetic single-channel recording
. Original schematic of cell-attached recording and whole-cell recording, with synthetic electric current traces and a single-channel current-voltage relation. The prescribed opening times are identical at and solely to compare amplitudes. These are not experimental data or a model of opening probability. Membrane potential means the actual voltage across the patch, not automatically the pipette command. Details.
The 1976 article Single-channel currents recorded from membrane of denervated frog muscle fibres describes an extracellular fire-polished pipette with a – opening and – electrical resistance. It contained saline and a channel-activating compound. Two separate intracellular electrodes supplied local voltage clamp of the muscle fibre; the patch amplifier measured local electric current. Cooling to – and hyperpolarization helped resolve elementary events. Figure 2 shows step-like pulses with a filter at and . Discrete amplitudes and overlapping events supported individual ion channel openings rather than a smoothly varying population response. This was neither whole-cell recording through the patch pipette nor current clamp. The specialized conditions improved visibility but limit generalization to warmer preparations; filtering can conceal brief openings.[ref]
For a new single-channel recording experiment, useful controls include a matched recording without the activating compound, controlled membrane potential, repeated seal tests, and an explicitly stated filter frequency response. These are proposed controls, not claims that every one was performed in that 1976 figure. Changing membrane potential tests the single-channel current-voltage relation; changing the recording filter tests whether a short pulse's apparent amplitude is an instrument artifact. A flat baseline establishes neither an absence of ion channels nor an absence of very brief events.
Patch pipette 2026-10-13
A patch pipette is the tapered glass, solution-filled probe used in patch clamp. Its electrode connects the solution to an amplifier, with another electrode referencing the bath. The open-tip electrical resistance differs from the much larger gigaohm seal electrical resistance. After break-in, a narrow or partly obstructed tip contributes to patch-clamp series resistance.
Whole-cell recording 2026-10-13
Whole-cell recording establishes intracellular electrical access by rupturing the membrane under a sealed patch pipette while retaining the gigaohm seal. Under adequate voltage clamp, the measured electric current combines contributions from accessible ion channels, membrane capacitance and seal leak current. Current clamp instead follows membrane potential while supplying a chosen electric current. Whole-cell recording is useful for linking a biological cell's total electrical response to its ion channels, but neither mode automatically controls distant dendrites or preserves the original cytosol.
In the 1981 methods demonstration, a bovine chromaffin biological cell was tested before and after patch rupture. Small voltage clamp steps produced a much larger capacitive transient after break-in. Integrating it gave for a cell; its decay indicated patch-clamp series resistance below . Depolarizing commands then revealed ionic electric currents. Separate current clamp recordings showed spontaneous action potentials. The comparison established access to the cell interior, rather than a claim that every pipette command equals membrane potential. Slower transients sometimes indicated incomplete rupture, and these small-cell results do not establish spatial control of a branched neuron.[ref]
Figure 1.
Synthetic whole-cell recording: patch-clamp series resistance and passive responses
. An original equivalent electrical circuit uses , and . The current clamp step and voltage clamp step are separate synthetic experiments. The passive model omits active ion channels, seal leak current, pipette capacitance and amplifier dynamics. Curves are calculations, not experimental measurements. Details.