1 A mathematical model has been developed which describes the conductive and kinetic properties of homotypic and heterotypic gap junction channels of vertebrates. 2 The model consists of two submodels connected in series. Each submodel simulates a hemichannel and consists of two conductances corresponding to a high (H) and low (L) conductance state and a switch, which simulates the voltage‐dependent channel gating. 3 It has been assumed that the conductances of the high state and low state vary exponentially with the voltage across the hemichannel. 4 The parameters of the exponentials can be derived from data of heterotypic or homotypic channels. As a result, the behaviour of heterotypic channels can be predicted from homotypic channel data and vice versa. 5 The two switches of a channel are governed by the voltage drop across the respective hemichannel. The switches of a channel work independently, thus giving rise to four conformational states, i.e. HH, LH, HL and LL. 6 The computations show that the dogma of a constant conductance for homotypic channels results from the limited physiological range of transjunctional voltages (Vj) and the kinetic properties of the channel, so a new fitting procedure is presented. 7 Simulation of the kinetic properties at the multichannel level revealed current time courses which are consistent with a contingent gating. 8 The calculations have also shown that the channel state LL is rare and of short duration, and hence easy to miss experimentally. 9 The design of the model has been kept flexible. It can be easily expanded to include additional features, such as channel substates or a closed state.
[1]
J. Stark,et al.
Modelling the Effect of Gap Junction Nonlinearities in Systems of Coupled Cells
,
1997
.
[2]
R. Bruzzone,et al.
Connections with connexins: the molecular basis of direct intercellular signaling.
,
1996,
European journal of biochemistry.
[3]
R. Weingart,et al.
Conductances and selective permeability of connexin43 gap junction channels examined in neonatal rat heart cells.
,
1997,
Circulation research.
[4]
K. Willecke,et al.
Biophysical properties of gap junction channels formed by mouse connexin40 in induced pairs of transfected human HeLa cells.
,
1995,
Biophysical journal.
[5]
R. Morris.
Foundations of cellular neurophysiology
,
1996
.
[6]
M. Bennett,et al.
Voltage gating and permeation in a gap junction hemichannel.
,
1996,
Proceedings of the National Academy of Sciences of the United States of America.
[7]
D C Spray,et al.
Kinetic properties of a voltage-dependent junctional conductance
,
1981,
The Journal of general physiology.
[8]
D. Spray,et al.
Exogenous Expression of Connexins for Physiological Characterization of Channel Properties: Comparison of Methods and Results
,
1995
.
[9]
R. Weingart,et al.
Biophysical properties of heterotypic gap junctions newly formed between two types of insect cells.
,
1997,
The Journal of physiology.