Reemerging role of cable properties in action potential initiation

GABAA receptors are found on the somatodendritic compartment and on the axon initial segment of many principal neurons. The function of axonal receptors remains obscure, although it is widely assumed that axonal receptors must have a strong effect on excitability. We found that activation of GABAA receptors on the dentate granule neuron axon initial segment altered excitability by depolarizing the voltage threshold for action potential initiation under conditions that minimally affected overall cell input resistance. In contrast, activation of somatic GABAA receptors strongly depressed the input resistance of granule neurons without affecting the voltage threshold of action potential initiation. Although these effects were observed over a range of intracellular chloride concentrations, average voltage threshold was unaffected when ECl rendered GABAA axon initial segment responses explicitly excitatory. A compartment model of a granule neuron confirmed these experimental observations. Low ambient agonist concentrations designed to activate granule neuron tonic currents did not stimulate axonal receptors sufficiently to raise voltage threshold. Using excitatory postsynaptic current (EPSC)-like depolarizations, we show physiological consequences of axonal versus somatic GABAA receptor activation. With axonal inhibition, individual excitatory postsynaptic potentials (EPSPs) largely retained their amplitude and time course, but EPSPs that were suprathreshold under basal conditions failed to reach threshold with GABAA activation. By contrast, somatic inhibition depressed individual EPSPs because of strong shunting. Our results suggest that axonal GABAA receptors have a privileged effect on voltage threshold and that two major measures of neuronal excitability, voltage threshold and rheobase, are differentially affected by axonal and somatic GABAA receptor activation.

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Somatic modulation of ectopic action potential initiation in distal axons

The Journal of Physiology ◽

10.1113/jp277012 ◽

2018 ◽

Vol 596 (21) ◽

pp. 5067-5068

Author(s):

Aurélie Fékété ◽

Dominique Debanne

Keyword(s):

Action Potential ◽

Action Potential Initiation ◽

Potential Initiation

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Determinants of action potential initiation in isolated rabbit atrial and ventricular myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.6.h1902 ◽

1998 ◽

Vol 274 (6) ◽

pp. H1902-H1913 ◽

Cited By ~ 8

Author(s):

David A. Golod ◽

Rajiv Kumar ◽

Ronald W. Joyner

Keyword(s):

Action Potential ◽

Ventricular Myocytes ◽

Cell Types ◽

Membrane Properties ◽

Resting Membrane Potential ◽

Isolated Cells ◽

Atrial Cells ◽

Ventricular Cells ◽

Action Potential Initiation ◽

Potential Initiation

Action potential conduction through the atrium and the ventricle of the heart depends on the membrane properties of the atrial and ventricular cells, particularly with respect to the determinants of the initiation of action potentials in each cell type. We have utilized both current- and voltage-clamp techniques on isolated cells to examine biophysical properties of the two cell types at physiological temperature. The resting membrane potential, action potential amplitude, current threshold, voltage threshold, and maximum rate of rise measured from atrial cells (−80 ± 1 mV, 109 ± 3 mV, 0.69 ± 0.05 nA, −59 ± 1 mV, and 206 ± 17 V/s, respectively; means ± SE) differed significantly ( P < 0.05) from those values measured from ventricular cells (−82.7 ± 0.4 mV, 127 ± 1 mV, 2.45 ± 0.13 nA, −46 ± 2 mV, and 395 ± 21 V/s, respectively). Input impedance, capacitance, time constant, and critical depolarization for activation also were significantly different between atrial (341 ± 41 MΩ, 70 ± 4 pF, 23.8 ± 2.3 ms, and 19 ± 1 mV, respectively) and ventricular (16.5 ± 5.4 MΩ, 99 ± 4.3 pF, 1.56 ± 0.32 ms, and 36 ± 1 mV, respectively) cells. The major mechanism of these differences is the much greater magnitude of the inward rectifying potassium current in ventricular cells compared with that in atrial cells, with an additional difference of an apparently lower availability of inward Na current in atrial cells. These differences in the two cell types may be important in allowing the atrial cells to be driven successfully by normal regions of automaticity (e.g., the sinoatrial node), whereas ventricular cells would suppress action potential initiation from a region of automaticity (e.g., an ectopic focus).

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