title: An examination of calcium current function on heterotopic neurons in hippocampal slices from rats exposed to methylazoxymethanol.
abstract: OBJECTIVE
  To study voltage-dependent calcium currents (VDCCs) on hippocampal heterotopic neurons by using whole-cell patch-clamp techniques in brain slices prepared from methylaxozymethanol (MAM)-exposed rats.
  
  
  METHODS
  Whole-cell voltage-clamp recordings were obtained from visually identified neurons in acute brain slices by using an infrared differential interference contrast (IR-DIC) video microscopy system. Heterotopic neurons were compared with normotopic pyramidal cells in hippocampal slices from MAM-exposed rats or CA1 pyramidal neurons in slices from controls.
  
  
  RESULTS
  Heterotopic neurons expressed a prominent VDCC, which exhibited a peak current maximum around -30 mV (holding potential, -60 mV) and an inactivation time constant of 48.2 +/- 2.4 ms (n = 91). VDCC peak current and inactivation time constants were similar for normotopic (n = 92) and CA1 pyramidal cells (n = 40). Pharmacologic analysis of VDCC, on heterotopic, normotopic, and CA1 pyramidal cells, revealed an approximately 70% blockade of peak Ca2+ current with nifedipine and amiloride (L- and T-type channel blockers, respectively). Inhibition of VDCC, for all three cell types, also was similar when more specific Ca2+ channel antagonists were used [e.g., omega-conotoxin GVIA (N-type), omega-agatoxin KT (P/Q-type), and sFTX-3.3 (P-type)]. VDCC modulation by norepinephrine (NE) or adrenergic receptor-specific agonists [clonidine (alpha2), isoproterenol (beta), and phenylephrine (alpha1)] was similar for heterotopic and CA1 pyramidal cells.
  
  
  CONCLUSIONS
  Heterotopic neurons do not appear to exhibit Ca2+ channel abnormalities that could contribute to the reported hyperexcitability associated with MAM-exposed rats.
authors.affiliation: Epilepsy Research Laboratory, Department of Neurological Surgery and The Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, California 94143, USA.
authors.forename: Maria Elisa
authors.initials: ME
authors.lastname: Calcagnotto
authors.forename: Scott C
authors.initials: SC
authors.lastname: Baraban
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002828:Choristoma / Q000139:chemically induced* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D005260:Female; D006624:Hippocampus / Q000002:abnormalities* / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D009421:Nervous System Malformations / Q000139:chemically induced* / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013723:Teratogens / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D013723:Teratogens; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol; D002118:Calcium