• Pharmacomechanical coupling- does not depend upon changes in membrane potential or calcium entry via the VOCC. • The rise of intracellular  Ca2+ is brought about by a combination of Ca2+ release from intracellular stores and Ca2+ entry through non-voltage gated channels, primarily receptor operated calcium channels or store operated Ca2+ channels • Ca2+ signal often similar to that seen in many non-excitable cells, consisting of an initial rise in [Ca 2+]i followed by a smaller, but sustained increase dependent upon Ca2+ entry from the extracellular space. • This secondary influx of Ca2+, in association with the process of Ca2+ sensitization whereby the contractile apparatus may be activated by near- resting levels of [Ca2+]i, allows muscles to maintain tone over prolonged periods in the presence of an agonist; occurs in tonic smooth muscle.