Slowing Effects of Dopamine and Calcium-channel Blockers on Frequency of Sodium Spikes in Rat Pars Intermedia Cells

1. Spontaneous discharge of action potentials (Na spikes) in cells isolated from rat pars intermedia was slowed or arrested by Co(2+), Ni(2+) or Mn(2+), which block voltage-dependent Ca channels in these cells. The amplitude of persisting spikes was undiminished. The effects resembled those of dopamine.2. Action potential frequency decreased when the Ca(2+) concentration was lowered to 0.1 mM and increased when the Ca(2+) concentration was raised from this level to 1 mM or 2 mM or when Ba(2+) (2 mM) was introduced. These effects, together with those of Co(2+), Ni(2+) and Mn(2+), are consistent with the possibility that Ca(2+) participates in the regulation of spike discharge.3. Verapamil, methoxyverapamil (D600), and nifedipine reduced the amplitude of the individual Na spikes in concentrations that had little effect on voltage-dependent Ca channels. Action potential frequency was comparatively little affected by these drugs.4. K(+) (15 mM) stimulated action potential frequency and this effect too was suppressed by dopamine or Co(2+).5. The effect which dopamine had of slowing spontaneous discharge, like the inhibitory effect on secretion, was blocked by metoclopramide. But otherwise the mechanism is unclear: dopamine blocked voltage-dependent Ca channels in some cells but not in most others.6. The effects of K(+) and Ba(2+) of eliciting spikes, the suppression of Na-spike discharge by Co(2+) and related Ca-channel blocking cations, and the unspecific effects of the organic ;Ca channel blockers', all have implications for the use of these substances as tools to analyse stimulus-secretion coupling.