1. Experimental studies employing whole cell patch recordings from freshly isolated olfactory sensory neurons of the salamander (Ambystoma tigrinum) yield much higher estimates of specific membrane resistance (Rm) than studies using conventional intracellular recordings from in situ neurons. Because Rm is critical for understanding information transfer in these cells, we have used computational methods to analyze the possible reasons for this difference. 2. Compartmental models were constructed for both the in situ and isolated neurons, using SABER, a general-purpose simulation program. For Rm in the in situ cell, we used a high value of 100,000 omega.cm2, as estimated in the whole cell recordings from isolated cells. A shunt across the cell membrane caused by the penetrating microelectrode was simulated by several types of shunt mechanisms, and its effects on lowering the apparent value of resting membrane potential (MP), input resistance (RN), and membrane time constant (tau m) and increasing the electrotonic length (L) were analyzed. 3. A good approximation of the electrotonic properties recorded intracellularly was obtained in the in situ model with high Rm combined with an electrode shunt consisting of Na and K conductances. A raised K conductance (1-5 nS) helps to maintain the resting MP while contributing to the increased conductance, which lowers RN and shortens the apparent tau m toward the experimental values. 4. Combined shunt resistances of 0.1-0.2 G omega (5-10 nS) gave the best fits with the experimental data. These shunts were two to three orders of magnitude smaller than the values reported from intracellular penetrations in muscle cells and motoneurons. This may be correlated with the smaller electrode tips used in the recordings from these small neurons. We thus confirm the prediction that even small values of electrode shunt have relatively large effects on the recorded electrotonic properties of small neurons, because of their high RN (2-5 G omega). 5. We have further explored the effects on electrotonic structure of a nonuniform Rm by giving higher Rm values to the distally located cilia compared with the proximal soma-dendritic region, as indicated by recent experiments. For the same RN, large increases in ciliary Rm above 100,000 omega.cm2 can be balanced by relatively small decreases below that value in soma-dendritic Rm. A high ciliary Rm appears to be a specialization for transduction of the sensory input, as reported also in photoreceptors and hair cells.
Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons
