Blockade of Ca2+ and K+ currents in bag cell neurons of Aplysia californica by dihydropyridine Ca2+ antagonists

Abstract

The effects of dihydropyridine calcium antagonists on whole-cell Ca2+ and K+ currents in the neurosecretory bag cells of the marine mollusc Aplysia californica have been investigated. Nifedipine and nisoldipine blocked bag cell Ca2+ currents with effects similar to those seen previously on Ca2+ currents in cardiac muscle: both compounds appeared to interact with Ca2+ channels when they were closed, open, and inactivated. Also, as seen in cardiac cells, nifedipine apparently binds with higher affinity to Ca2+ channels when they are inactivated than when they are either closed or open. Nifedipine and nisoldipine also inhibited 2 outward K+ currents in bag cells: the “delayed rectifier” (IK) and the “A” (IA) currents. Half-maximal blockade of Ca2+ currents occurred at approximately 1.4 microM nifedipine, compared to approximately 3–5 microM for half-maximal blockade of IK and IA. The effects of these compounds on bag cell Ca2+ and K+ currents are interpreted and discussed here in terms of the “modulated receptor” model of drug action. In contrast, however, no measurable effects of nifedipine or nisoldipine were seen on Ca2+ (and/or K+) currents in several vertebrate neuronal cell types. Our results suggest that there are likely to be structural and/or conformational variations in Ca2+ channels in different cells, tissues, and/or species and also that, in some cells, Ca2+ and K+ channels might be structurally similar. These findings also suggest, therefore, that if dihydropyridine binding is used to identify Ca2+ channels, care should be taken to ensure that binding correlates closely with the Ca2+ channels of interest.

Contribution of a non‐inactivating potassium current to the resting membrane potential of fusion‐competent human myoblasts.

“…Newly formed myotubes also possess this 'K(ni) current (data not shown) but no similar current was observed in proliferating myoblasts (Hamann et al 1994 (Valmier, Richard, Devic, Nargeot, Simmoneau & Baldy, 1991). In Aplysia bag cell neurones, potassium currents are blocked with a Kd of 3-5 ,uM (Nerbonne & Gurney, 1987), similar to the Kd of nifedipine for the blocking of IK(dr) in prefused myoblasts. More recently, it has been shown that the A-current of bovine adrenal cells is also affected by DHP (Mlinar & Enyeart, 1994 (Zhao et al 1994).…”

Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture

“…We found in previous voltage-clamp experiments that 10 HIM nitrendipine blocks about 90% of L-type current in sensory neurons (Eliot et al, 1993). Unlike their action in vertebrate neurons, dihydropyridine antagonists do not require depolarization to block Ca2+ currents effectively in Aplysia neurons (Nerbonne and Gurney, 1987;Edmonds et al, 1990).…”

Cloning and Functional Expression of a Voltage-gated Calcium Channel α1 Subunit from Jellyfish

“…The Ca 2ϩ current in Paramecium is unaffected by DHPs (43), and neuronal Ca 2ϩ currents in the hydrozoan jellyfish Polyorchis (21) and the flatworm Bdelloura (55) are only partially blocked by 10 -100 M nifedipine (although these Ca 2ϩ currents may not be gated by L-type channel homologues). Molluscs are the earliest organisms in which potent block of Ca 2ϩ currents by DHPs has been reported (56), although the current is unaffected by racemic BayK 8644. The present results demonstrate that the actions of DHPs, which are generally used to define a current as L-type, may not reliably identify L-type channel homologues in lower organisms.…”