= Patch clamp
{wiki}
<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.
\Image[/patch-clamp-configurations-and-unitary-current.png]
{title=<Patch clamp> configurations and synthetic <single-channel recording>}
{description=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 $-80$ and $-40\,\mathrm{mV}$ 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.}
The 1976 article https://cenl.ucsd.edu/psych506A/papers/neher-sakmann%2Bsingle-channel-currents-membrane-denervated-frog-muscle%2BNature%2B1976.pdf[Single-channel currents recorded from membrane of denervated frog muscle fibres] describes an extracellular fire-polished pipette with a $3$–$5\,\mu\mathrm m$ opening and $2$–$5\,\mathrm{M\Omega}$ <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 $6$–$8\,{}^\circ\mathrm C$ and <hyperpolarization> helped resolve elementary events. Figure 2 shows step-like pulses with a $200\,\mathrm{Hz}$ filter at $-120\,\mathrm{mV}$ and $8\,{}^\circ\mathrm C$. 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.<Single-channel currents recorded from membrane of denervated frog muscle fibres by Erwin Neher and others>[p. 800, Figures 1–2 and accompanying experimental conditions]{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.
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