1. We studied the effect of cholinergic agonists on motoneurons of the lobster cardiac ganglion under voltage clamp. 2. In unclamped neurons, acetylcholine (ACh) caused a depolarization and increase in burst potential frequency. By the use of nicotinic and muscarinic agonists, we determined that both types of receptors are present on the neurons. We therefore used specific muscarinic agonists to further study ionic mechanisms underlying the muscarinic cholinergic current (Imch). 3. Muscarinic agonists produced detectable inward current at doses above 10(-6) M, and maximum effect was seen at doses above 10(-3) M. 4. Imch was voltage-dependent. When the membrane holding potential was shifted to levels negative to the resting potential, the response declined, nulling but not reversing at -80 to -100 mV. The response enlarged with membrane depolarization, reaching a maximum at between -30 and -10 mV. With further depolarization, the response declined and then reversed at potentials around +20 mV. 5. The muscarinic response varied as a function of extracellular Na+ concentration and was completely blocked in Na+-free solutions. The relationship between response amplitude and external Na+ was well described by the electrodiffusion equation for Na+ driving force. 6. Imch amplitude also varied as a function of extracellular potassium concentration, becoming larger with low external K+ and smaller at higher concentrations. Shifting the Cl- equilibrium potential did not affect the properties of the Imch. 7. Tetrodotoxin (TTX) had no effect on Imch. In concentrations of 1-10 mM, such K+-channel blocking agents as Ba2+, Cs+, 4-aminopyridine (4-AP), or tetraethylammonium (TEA), and such Ca2+-channel blockers as Co2+ or Mn2+, when applied externally, did not suppress Imch. Above 30 mM, TEA did inhibit the response, and combinations of K+-channel blocking agents, each at concentrations insufficient alone to block the current, also inhibited Imch. 8. Current-voltage (I-V) curves obtained during muscarinic agonist perfusion consistently crossed the control I-V curves at a mean membrane potential of +24 mV. The reversal potential shifted to a more negative value in low extracellular Na+. 9. Although no reversal of Imch was seen when agonists were applied to cells clamped at negative holding potentials, the averaged curve of Imch, obtained by subtracting control ramp I-V curves from those obtained in the presence of agonist, did show a small net outward current at membrane potentials negative to -100 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
Comparative Pharmacodynamics of Eight Calcium Channel Blocking Agents in Japanese Essential Hypertensive Patients.
