Mathematical model of vertebrate gap junctions derived from electrical measurements on homotypic and heterotypic channels

Authors


Corresponding authors R. Weingart: Department of Physiology, University of Bern, Bühlplatz 5, 3012 Bern, Switzerland. Email: weingart@pyl.unibe.ch

Abstract

  • 1A mathematical model has been developed which describes the conductive and kinetic properties of homotypic and heterotypic gap junction channels of vertebrates.
  • 2The 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.
  • 3It has been assumed that the conductances of the high state and low state vary exponentially with the voltage across the hemichannel.
  • 4The 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.
  • 5The 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.
  • 6The 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.
  • 7Simulation of the kinetic properties at the multichannel level revealed current time courses which are consistent with a contingent gating.
  • 8The calculations have also shown that the channel state LL is rare and of short duration, and hence easy to miss experimentally.
  • 9The 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.

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