= Cytosol dialysis
<Cytosol dialysis> is exchange between the <cytosol> and pipette solution through the opening used in conventional <whole-cell recording>. <Diffusion> can change <ion> <concentrations> and dilute soluble regulators of <ion channels>. A diminishing response can therefore reflect the recording's alteration of the <biological cell>, rather than the experimental treatment.
A direct motivating example is the 1988 article https://pubmed.ncbi.nlm.nih.gov/2459299/[Muscarinic activation of ionic currents measured by a new whole-cell recording method]. In rat lacrimal gland <biological cells>, the <acetylcholine> response in conventional <whole-cell recording> lasted about five minutes. With a pore-forming substance in the <patch pipette> instead of open break-in, the response remained undiminished after one hour. The readout was activation of <calcium>-activated <potassium> and $\mathrm{Cl}^-$ <ion> <electric currents>; preserving the response supported a role for retained cytoplasmic components. The authors also tested the substance extracellularly and observed reversible increases in <cation> <electrical conductance>. This comparison motivates <perforated patch recording>, but does not show that every intracellular constituent or every <ion channel> response is preserved. <Muscarinic activation of ionic currents measured by a new whole-cell recording method by Richard Horn and others>{ref}
Practical controls are matched pipette and bath compositions, recording elapsed time after break-in, time-matched untreated preparations, and tracking both <patch-clamp series resistance> and baseline leakage. Comparing conventional <whole-cell recording> with <perforated patch recording> can separate loss of soluble components from an intended treatment effect, but only if electrical access is characterized in both. These are controls suggested by the mechanisms above, not a new set of measured results.
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