Activating a neuron generally means depolarizing the neuron, sometimes depolarizing enough to trigger an action potential. In general, molecules activate neurons by binding to their cognate receptors in the neuron cell membrane. Sometimes the receptor is, itself, an ion channel. Other times the receptor initiates a cascade of events in the neuron's cytosol that end up modifying the cytoplasmic portion of an ion channel and thus opening the channel. In both cases, the channel is usually specific for positively charged ions (cations) (e.g. Na+ or Ca2+) whose concentration is greater outside the neuron than in the neuron's cytosol. Activation results when these cation channels open and allow positively charged ions to flow into the neuron. This entry of positive charge reduces the neuron's cell membrane potential, making the potential less negative. If enough positive charge enters, the neuron may be depolarized enough to trigger an action potential on the neuron's axon. This is what is usually meant by activating a neuron. It depends on the three-dimensional structure of the molecule (often a neurotransmitter) and the structure of the receptor. The binding of a signaling molecule to its receptor is usually non-covalent, often mediated by hydrogen bonds.