The shape of interspike interval (ISI) trajectory is one of the main electrophysiological properties that are related to the pattern of neural activity. Here, to study the relationship between ISI profile and firing pattern, conventional current clamp experiments performed in neurons of snail Caucasotachea atrolabiata. In control conditions, most neurons showed spontaneous rhythmic firing. The regular action potentials were interspaced with convex after hyperpolarizations (AHP) showing fast and medium components. High frequency trains of evoked action potentials showed spike frequency adaptation (SFA) and were followed by a prominent slow post stimulus AHP in a concave profile. Both apamin, a selective antagonist of slow Ca2+-dependent K+ channels, and nifedipine, an L-type Ca2+ channel blocker, suppressed the medium component of single-spike AHP and disrupted the rhythmic activity, which was evidenced as a significant increase in the coefficient of variation (CV) of ISI, but did not affect neither SFA nor post stimulus AHP. The strong correlation between firing rate and both action potential height and maximum raising slope during evoked activity, supported the importance of Na+ channel inactivation rather than ISI modulation by Ca2+ accumulation in the generation of SFA. When recording performed in Ca2+ Ringer, an afterdepolarization on the falling phase of the Ca2+ spikes was occasionally present and could be upmodulated by activation of protein kinase C. This in turn was associated with a decrease in the firing regularity. Findings show that the normal ISI profile is essential for the control of rhythmic spontaneous activity but is not involved in SFA.