THE MODE OF SODIUM DEPENDENCY OF THE ADRENERGIC NEURON AMINE CARRIER. EVIDENCE FOR A SECOND, SODIUM- DEPENDENT, OPTICALLY SPECIFIC AND RESERPINE-SENSITIVE SYSTEM

¹ Department of Pharmacology, University of Texas Southwestern Medical School, Dallas, Texas

The uptake of l- or d- metaraminol (l-MA, d-MA) by adrenergic neurons of rabbit heart slices is Na⁺-dependent. Kinetic studies show that apparent K m'S of uptake of both optical isomers are unchanged by altering [Na⁺] between 148.4 and 37.1 mM, suggesting that the Na⁺ requirement of the membrane amine carrier is stoichiometric in nature. Plotting d-MA uptake against [Na⁺] resulted in a single linear function going through the origin, whereas a similar plot of l-MA uptake resulted in a biphasic function. Reserpine enhanced the inhibitory effect of lowered [Na⁺] on l-MA uptake, but did not affect d-MA uptake. One phase of the i-MA uptake vs. [Na⁺] curve was abolished by reserpine, resulting in a single linear function. Although the apparent K_m of l-MA uptake was unaltered at [Na⁺] between 37.1 and 148.4 mM, a K_m 4 times lower was observed at 20 mM Na⁺. Desipramine was 20 times less effective in blocking l-MA uptake at 20 mM Na⁺ as compared with 148.4 mM Na⁺, but cold (4°C) blocked uptake completely. The results suggest the existence of a second, Na⁺-dependent, but optically specific, reserpine-sensitive uptake mechanism, requiring only low [Na⁺], which may function both intraneuronally and at the neuron membrane.