Final answer:
The extracellular concentration of potassium (K+) ions most significantly affects the resting membrane potential, with changes in K+ levels influencing the charge balance across the neuron's cell membrane.
Step-by-step explanation:
A change in the extracellular concentration of potassium (K+) ions has the greatest effect on the resting membrane potential. The resting membrane potential, typically between -50 mV to -70 mV, is predominantly controlled by the differential concentration of potassium ions across the cell membrane. Neurons have a high concentration of K+ inside and a lower concentration outside. The movement of K+ out of the neuron, more than the influx of sodium ions (Na+), creates a net negative charge inside the cell, which is essential for maintaining the resting membrane potential. During periods of increased permeability to Na+, such as when Na+ channels open, these ions enter the cell down their concentration gradient, leading to depolarization, which is a move toward a less negative membrane potential.