The synapses between vertebrate motor neurons and muscle cells are always excitatory. The motor end plates always respond to ACh with a graded potential that is less negative than the resting potential (depolarization). However, synapses between neurons are frequently inhibitory; such a synapse causes hyperpolarization of the postsynaptic membrane or simply makes it less likely that membrane potential will reach threshold for the voltage gated Na⁺ channels. For example, there are more Cl^– ions outside than inside the cell. However, in a mammalian neuron the equilibrium potential for Cl^– is around –60mV. Given a resting potential that is also around –60 mV, opening of Cl^– channels will not hyperpolarize the membrane, but if these channels are open, it will make it more difficult to raise the membrane potential to the threshold for the voltage gated Na⁺ channels.

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Recall that most neurons have many dendrites. Axon terminals from many other neurons can form synapses with those dendrites and with the cell body. The axon terminals of different presynaptic neurons can store and release different neurotransmitters, and the cell membrane of the dendrites and cell body of a postsynaptic neuron can have receptors for a variety of neurotransmitters. The mix of synaptic activity impinging on a neuron will cause it to have a graded membrane potential that can be either more positive or more negative than its resting potential.