We investigated the noise levels in cell-attached patch capacitance recordings with a lock-in amplifier. The capacitance noise level decreases with increasing sine wave frequency up to 20–40 kHz. With a 20-mV rms sine wave the rms noise level above 8 kHz is <50 aF. With increasing sine wave amplitudes a further reduction down to 14 aF could be achieved. Capacitance measurements with a lock-in amplifier may also be used to measure the conductance of fusion pores connecting the vesicular lumen to the extracellular space. It is estimated that at noise levels of 14 aF fusion pore conductances between 20 pS and 700 pS may be resolved in vesicles with 380-aF capacitance by using a 50-kHz sine wave. This corresponds to vesicles with a ∼110-nm diameter. It is suggested that with low-noise techniques fusion pores may be detectable in vesicles approaching the size of large synaptic vesicles.
