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Patch-clamp series resistance, also called patch-clamp access resistance, is the effective electrical resistance between the pipette's sensed voltage and the cell interior. It includes tip access and any remaining obstruction after break-in. For injected electric current $I$ into the biological cell, an ideal resistive access path givesThus $1\mathrm{nA}$ through $20\mathrm{M\Omega }$ produces a $20\mathrm{mV}$ difference: a substantial possible voltage clamp error. The electric current in this equation is the access-path current, excluding any bypass seal leak current. In current clamp, the same access drop contaminates the pipette voltage during injection. Bridge compensation subtracts an estimated $I{R}_s$; an estimate that changes during recording leaves an error.

An independent passive voltage clamp calculation makes both speed and error visible. Write $v=V-E_L$ and $v_p=V_p-E_L$, with fixed leak reversal potential $E_L$, constant membrane electrical resistance $R_m$ and membrane capacitance $C_m$. Assume an ideal command at the pipette node and omit seal leak current and pipette capacitance. Electric charge conservation givesFor a step $v_p=\Delta V$ from $v(0)=0$, the ordinary differential equation givesWith the figure's parameters and $\Delta V=10\mathrm{mV}$, the time constant is $0.909\mathrm{ms}$, the final membrane rise is $9.091\mathrm{mV}$, and access-path electric current falls from $500$ to $45.45\mathrm{pA}$. Only when $R_m\gg R_s$ does the time constant approach $R_s{C}_m$ and the final voltage approach the command. Actual voltage clamp also depends on amplifier feedback control and the space clamp problem.

The space clamp problem is the failure to maintain the commanded membrane potential throughout a spatially extended biological cell. A soma voltage clamp can coexist with substantial voltage changes in distant dendrites or an axon. Reducing patch-clamp series resistance improves access at the recording site, but does not eliminate electrical separation within the neuron.