Impedance analysis of a tight epithelium using a distributed resistance model.
This paper develops techniques for equivalent circuit analysis of tight epithelia by alternating-current impedance measurements, and tests these techniques on rabbit urinary bladder. Our approach consists of measuring transepithelial impedance, also measuring the DC voltage-divider ratio with a microelectrode, and extracting values of circuit parameters by computer fit of the data to an equivalent circuit model. We show that the commonly used equivalent circuit models of epithelia give significant misfits to the impedance data, because these models (so-called "lumped models") improperly represent the distributed resistors associated with long and narrow spaces such as lateral intercellular spaces (LIS). We develop a new "distributed model" of an epithelium to take account of these structures and thereby obtain much better fits to the data. The extracted parameters include the resistance and capacitance of the apical and basolateral cell membranes, the series resistance, and the ratio of the cross-sectional area to the length of the LIS. The capacitance values yield estimates of real area of the apical and basolateral membranes. Thus, impedance analysis can yield morphological information (configuration of the LIS, and real membrane areas) about a living tissue, independently of electron microscopy. The effects of transport-modifying agents such as amiloride and nystatin can be related to their effects on particular circuit elements by extracting parameter values from impedance runs before and during application of the agent. Calculated parameter values have been validated by independent electrophysiological and morphological measurements.
D000818:Animals; D004553:Electric Conductivity; D004848:Epithelium / Q000502:physiology*; D008433:Mathematics; D008839:Microelectrodes; D008954:Models, Biological; D011817:Rabbits; D001743:Urinary Bladder / Q000502:physiology
Proc R Soc Lond B Biol Sci. 1964 Apr 14;160:69-123
14142170
J Ultrastruct Res. 1963 Aug;39:1-9
14065355
J Gen Physiol. 1962 Mar;45:625-41
13882704
Bull Math Biol. 1979;41(2):163-81
760880
J Membr Biol. 1976 AUG 27;28(1):1-40
9512
Am J Physiol. 1977 Mar;232(3):F187-95
320880
J Gen Physiol. 1977 Oct;70(4):427-40
915470
Gastroenterology. 1977 Oct;73(4 Pt 2):970
902959
Biophys J. 1977 Jan;17(1):57-93
831857
J Membr Biol. 1976 AUG 27;28(1):41-70
966267
J Gen Physiol. 1974 Apr;63(4):460-91
4544879
Biophys J. 1965 Jul;5(4):591-606
5861708
J Membr Biol. 1975;22(2):165-81
1079877
Mol Pharmacol. 1972 Mar;8(2):222-9
4623567
J Gen Physiol. 1974 Apr;63(4):432-59
4820090
J Membr Biol. 1972;8(3):259-301
5084117
Gastroenterology. 1975 Dec;69(6):1208-22
1193322
Biophys J. 1975 Nov;15(11):1161-4
1201332
Am J Physiol. 1970 Jul;219(1):184-92
5424843