What causes the preliminary changes in resting membrane potential in neurons?

Question

Background: The neuron's membrane resting potential is maintained at a certain voltage. The neuron has a lipid bilayer with certain protein channels which allow the movement of ions in both directions (in and out). Some of these protein channels are gated by:

1) mechanical changes (stretching, pressure, etc)

2) voltage changes- regulated by electrical signals (transport of Na+, K+ through protein channels)

3) Ligands (neurotransmitters, etc)

(Guyton and Hall, Textbook of Medical Physiology, 2016)

Question: If action potentials are brought about by voltage-gated channels which are activated by the change in voltage, what brings about this change in voltage which activates voltage-gated channels?

It sounds a bit convoluted. Here's a quote from Wikipedia's Membrane Potential page:

Because voltage-gated ion channels are controlled by the membrane potential, while the membrane potential itself is influenced by these same ion channels, feedback loops that allow for complex temporal dynamics arise, including oscillations and regenerative events such as action potentials.

Hopefully this quote will help to communicate my confusion.

Answer 1

You have already listed two possibilities:

1) mechanical changes (stretching, pressure, etc)

and

3) Ligands (neurotransmitters, etc)

In the central nervous system, ligands and in particular neurotransmitters are going to be the overwhelming cause of most initial depolarization. Ligand-gated ion channels are the simplest mechanism: some examples include AMPA receptors, GABA-A receptors, and nicotinic acetylcholine receptors, but it is also possible to change the membrane potential via second messenger systems that open or close other channels.

In the periphery and in sensory organs, sensory-evoked potentials can be caused by mechanical gating, as you mention, as well as by specialized channels that respond to particular stimuli, for example the TRP family which includes channels sensitive to temperature (for example TRPV1, which responds to heat and also responds to capsaicin, the chemical that makes chili peppers 'hot') and to certain chemicals in food (resulting in taste).

The other category you missed is that some cells generate a spontaneous depolarization because they contain channels that are activated around the resting potential (and/or potassium channels that close, which also depolarizes the membrane). This is crucial for the cardiac pacemaker but can also be found in the central nervous system in some cell types.