Role of N- and L-type calcium channels in depolarization-induced activation of tyrosine hydroxylase and release of norepinephrine by sympathetic cellbodies and nerve terminals

Multiple types of voltage-activated calcium (Ca2+) channels are present in all nerve cells examined so far; however, the underlying functional consequ ences of their presence is often unclear. We have examined the contribution of Ca2+ influx through N- and L- type voltage-activated Ca2+ channels in s ympathetic neurons to the depolarization-induced activation of tyrosine hyd roxylase (TH), the rate-limiting enzyme in norepinephrine (NE) synthesis, a nd the depolarization-induced release of NE. Superior cervical ganglia (SCG ) were decentralized 4 days prior to their use to eliminate the possibility of indirect effects of depolarization via preganglionic nerve terminals. T he presence of both omega-conotoxin GVIA (1 mu M), a specific blocker of N- type channels, and nimodipine (1 mu M), a specific blocker of L-type Ca2+ c hannels, was necessary to inhibit completely the stimulation of TH activity by 55 mM K+, indicating that Ca2+ influx through both types of channels co ntributes to enzyme activation. In contrast, K+ stimulation of TH activity in nerve fibers and terminals in the iris could be inhibited completely by omega-conotoxin GVIA alone and was unaffected by nimodipine as previously s hown. K+ stimulation of NE release from both ganglia and irises was also bl ocked completely when omega-conotoxin GVIA was included in the medium, whil e nimodipine had no significant effect in either tissue, These results indi cate that particular cellular processes in specific areas of a neuron are d ifferentially dependent on Ca2+ influx through N- and L-type Ca2+ channels. (C) 1999 John Wiley & Sons, Inc.