Abstract
High-resolution measurement of membrane capacitance in the whole-cell-recording configuration can be used to detect small changes in membrane surface area that accompany exocytosis and endocytosis. We have investigated the noise of membrane capacitance measurements to determine the fundamental limits of resolution in actual cells in the whole-cell mode. Two previously overlooked sources of noise are particularly evident at low frequencies. The first noise source is accompanied by a correlation between capacitance estimates, whereas the second noise source is due to "1/f-like" current noise. An analytic expression that summarizes the noise from thermal and 1/f sources is derived, which agrees with experimental measurements from actual cells over a large frequency range. Our results demonstrate that the optimal frequencies for capacitance measurements are higher than previously believed. Finally, we demonstrate that the capacitance noise at high frequencies can be reduced by compensating for the voltage drop of the sine wave across the series resistance.
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Selected References
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- Barnett D. W., Misler S. An optimized approach to membrane capacitance estimation using dual-frequency excitation. Biophys J. 1997 Apr;72(4):1641–1658. doi: 10.1016/S0006-3495(97)78810-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chow R. H., Klingauf J., Heinemann C., Zucker R. S., Neher E. Mechanisms determining the time course of secretion in neuroendocrine cells. Neuron. 1996 Feb;16(2):369–376. doi: 10.1016/s0896-6273(00)80054-9. [DOI] [PubMed] [Google Scholar]
- Fidler N., Fernandez J. M. Phase tracking: an improved phase detection technique for cell membrane capacitance measurements. Biophys J. 1989 Dec;56(6):1153–1162. doi: 10.1016/S0006-3495(89)82762-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gillis K. D. Admittance-based measurement of membrane capacitance using the EPC-9 patch-clamp amplifier. Pflugers Arch. 2000 Mar;439(5):655–664. doi: 10.1007/s004249900173. [DOI] [PubMed] [Google Scholar]
- Gillis K. D., Mossner R., Neher E. Protein kinase C enhances exocytosis from chromaffin cells by increasing the size of the readily releasable pool of secretory granules. Neuron. 1996 Jun;16(6):1209–1220. doi: 10.1016/s0896-6273(00)80147-6. [DOI] [PubMed] [Google Scholar]
- Horrigan F. T., Bookman R. J. Releasable pools and the kinetics of exocytosis in adrenal chromaffin cells. Neuron. 1994 Nov;13(5):1119–1129. doi: 10.1016/0896-6273(94)90050-7. [DOI] [PubMed] [Google Scholar]
- Lindau M., Neher E. Patch-clamp techniques for time-resolved capacitance measurements in single cells. Pflugers Arch. 1988 Feb;411(2):137–146. doi: 10.1007/BF00582306. [DOI] [PubMed] [Google Scholar]
- Lollike K., Borregaard N., Lindau M. The exocytotic fusion pore of small granules has a conductance similar to an ion channel. J Cell Biol. 1995 Apr;129(1):99–104. doi: 10.1083/jcb.129.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moser T., Neher E. Estimation of mean exocytic vesicle capacitance in mouse adrenal chromaffin cells. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6735–6740. doi: 10.1073/pnas.94.13.6735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neher E., Marty A. Discrete changes of cell membrane capacitance observed under conditions of enhanced secretion in bovine adrenal chromaffin cells. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6712–6716. doi: 10.1073/pnas.79.21.6712. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pusch M., Neher E. Rates of diffusional exchange between small cells and a measuring patch pipette. Pflugers Arch. 1988 Feb;411(2):204–211. doi: 10.1007/BF00582316. [DOI] [PubMed] [Google Scholar]
- Rech F., Rohlícek V., Schmid A. A method of resolution improvement by the measurement of cell membrane capacitance. Physiol Res. 1996;45(5):421–425. [PubMed] [Google Scholar]
- Zhou Z., Neher E. Mobile and immobile calcium buffers in bovine adrenal chromaffin cells. J Physiol. 1993 Sep;469:245–273. doi: 10.1113/jphysiol.1993.sp019813. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zupancic G., Kocmur L., Veranic P., Grilc S., Kordas M., Zorec R. The separation of exocytosis from endocytosis in rat melanotroph membrane capacitance records. J Physiol. 1994 Nov 1;480(Pt 3):539–552. doi: 10.1113/jphysiol.1994.sp020382. [DOI] [PMC free article] [PubMed] [Google Scholar]